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1.
New Phytol ; 241(6): 2435-2447, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38214462

RESUMO

Radiation use efficiency (RUE) is a key crop adaptation trait that quantifies the potential amount of aboveground biomass produced by the crop per unit of solar energy intercepted. But it is unclear why elite maize and grain sorghum hybrids differ in their RUE at the crop level. Here, we used a non-traditional top-down approach via canopy photosynthesis modelling to identify leaf-level photosynthetic traits that are key to differences in crop-level RUE. A novel photosynthetic response measurement was developed and coupled with use of a Bayesian model fitting procedure, incorporating a C4 leaf photosynthesis model, to infer cohesive sets of photosynthetic parameters by simultaneously fitting responses to CO2 , light, and temperature. Statistically significant differences between leaf photosynthetic parameters of elite maize and grain sorghum hybrids were found across a range of leaf temperatures, in particular for effects on the quantum yield of photosynthesis, but also for the maximum enzymatic activity of Rubisco and PEPc. Simulation of diurnal canopy photosynthesis predicted that the leaf-level photosynthetic low-light response and its temperature dependency are key drivers of the performance of crop-level RUE, generating testable hypotheses for further physiological analysis and bioengineering applications.


Assuntos
Fotossíntese , Luz Solar , Temperatura , Teorema de Bayes , Fotossíntese/fisiologia , Folhas de Planta , Zea mays
2.
Plant Cell Environ ; 46(1): 23-44, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36200623

RESUMO

Photosynthetic manipulation provides new opportunities for enhancing crop yield. However, understanding and quantifying the importance of individual and multiple manipulations on the seasonal biomass growth and yield performance of target crops across variable production environments is limited. Using a state-of-the-art cross-scale model in the APSIM platform we predicted the impact of altering photosynthesis on the enzyme-limited (Ac ) and electron transport-limited (Aj ) rates, seasonal dynamics in canopy photosynthesis, biomass growth, and yield formation via large multiyear-by-location crop growth simulations. A broad list of promising strategies to improve photosynthesis for C3 wheat and C4 sorghum were simulated. In the top decile of seasonal outcomes, yield gains were predicted to be modest, ranging between 0% and 8%, depending on the manipulation and crop type. We report how photosynthetic enhancement can affect the timing and severity of water and nitrogen stress on the growing crop, resulting in nonintuitive seasonal crop dynamics and yield outcomes. We predicted that strategies enhancing Ac alone generate more consistent but smaller yield gains across all water and nitrogen environments, Aj enhancement alone generates larger gains but is undesirable in more marginal environments. Large increases in both Ac and Aj generate the highest gains across all environments. Yield outcomes of the tested manipulation strategies were predicted and compared for realistic Australian wheat and sorghum production. This study uniquely unpacks complex cross-scale interactions between photosynthesis and seasonal crop dynamics and improves understanding and quantification of the potential impact of photosynthesis traits (or lack of it) for crop improvement research.


Assuntos
Nitrogênio , Água , Austrália
3.
Compr Rev Food Sci Food Saf ; 22(5): 4053-4073, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37458307

RESUMO

It has been suggested that amylopectin can contain small but significant amounts of extra-long chains (ELCs), which could affect functional properties, and also would have implications for the mechanism of starch biosynthesis. However, current evidence for the existence of ELCs is ambiguous. The amylose/amylopectin separation and the characterization techniques used for the investigation of ELCs are reviewed, problems in those techniques are examined, and studies of ELCs of amylopectin are discussed. A model for the biosynthesis of amylopectin chains in terms of conventional biosynthesis enzymes, which provides an excellent fit to a large amount of experimental data, is used to provide a rigorous definition of ELCs. In addition, current investigations of ELCs, involving separation, is hindered by the lack of a method to quantitatively separate all the amylopectin from starch without any traces of residual amylose (which would have long chains). Unambiguous evidence for the existence of ELCs can be obtained using two-dimensional (2D) characterization, these dimensions being the degree of polymerization of a chain and the size of the whole molecule. Available 2D data indicate that there are no ELCs present in currently detectable quantities in native rice starches. However, concluding this more rigorously requires improvements in the resolution of current 2D methods.


Assuntos
Amilopectina , Oryza , Amilose , Amido
4.
J Exp Bot ; 73(3): 801-816, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-34698817

RESUMO

Developing sorghum genotypes adapted to different light environments requires understanding of a plant's ability to capture light, determined through leaf angle specifically. This study dissected the genetic basis of leaf angle in 3 year field trials at two sites, using a sorghum diversity panel (729 accessions). A wide range of variation in leaf angle with medium heritability was observed. Leaf angle explained 36% variation in canopy light extinction coefficient, highlighting the extent to which variation in leaf angle influences light interception at the whole-canopy level. This study also found that the sorghum races of Guinea and Durra consistently having the largest and smallest leaf angle, respectively, highlighting the potential role of leaf angle in adaptation to distinct environments. The genome-wide association study detected 33 quantitative trait loci (QTLs) associated with leaf angle. Strong synteny was observed with previously detected leaf angle QTLs in maize (70%) and rice (40%) within 10 cM, among which the overlap was significantly enriched according to χ2 tests, suggesting a highly consistent genetic control in grasses. A priori leaf angle candidate genes identified in maize and rice were found to be enriched within a 1-cM window around the sorghum leaf angle QTLs. Additionally, protein domain analysis identified the WD40 protein domain as being enriched within a 1-cM window around the QTLs. These outcomes show that there is sufficient heritability and natural variation in the angle of upper leaves in sorghum which may be exploited to change light interception and optimize crop canopies for different contexts.


Assuntos
Sorghum , Grão Comestível/genética , Estudo de Associação Genômica Ampla , Folhas de Planta/genética , Locos de Características Quantitativas/genética , Sorghum/genética
5.
Theor Appl Genet ; 135(9): 3057-3071, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35933636

RESUMO

KEY MESSAGE: Leaf width was correlated with plant-level transpiration efficiency and associated with 19 QTL in sorghum, suggesting it could be a surrogate for transpiration efficiency in large breeding program. Enhancing plant transpiration efficiency (TE) by reducing transpiration without compromising photosynthesis and yield is a desirable selection target in crop improvement programs. While narrow individual leaf width has been correlated with greater intrinsic water use efficiency in C4 species, the extent to which this translates to greater plant TE has not been investigated. The aims of this study were to evaluate the correlation of leaf width with TE at the whole-plant scale and investigate the genetic control of leaf width in sorghum. Two lysimetry experiments using 16 genotypes varying for stomatal conductance and three field trials using a large sorghum diversity panel (n = 701 lines) were conducted. Negative associations of leaf width with plant TE were found in the lysimetry experiments, suggesting narrow leaves may result in reduced plant transpiration without trade-offs in biomass accumulation. A wide range in width of the largest leaf was found in the sorghum diversity panel with consistent ranking among sorghum races, suggesting that environmental adaptation may have a role in modifying leaf width. Nineteen QTL were identified by genome-wide association studies on leaf width adjusted for flowering time. The QTL identified showed high levels of correspondence with those in maize and rice, suggesting similarities in the genetic control of leaf width across cereals. Three a priori candidate genes for leaf width, previously found to regulate dorsoventrality, were identified based on a 1-cM threshold. This study provides useful physiological and genetic insights for potential manipulation of leaf width to improve plant adaptation to diverse environments.


Assuntos
Sorghum , Grão Comestível/genética , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Folhas de Planta/genética , Transpiração Vegetal/genética , Sorghum/genética , Água/fisiologia
6.
Breast Cancer Res Treat ; 168(2): 501-511, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29247440

RESUMO

PURPOSE: Breast tumors from young women under the age of 40 account for approximately 7% of cases and have a poor prognosis independent of established prognostic factors. We evaluated the patient population served by the Military Health System, where a disproportionate number of breast cancer cases in young women are seen and treated in a single universal coverage healthcare system. METHODS: The Military Health System Repository and the DoD Central Registration databases were used to identify female breast cancer patients diagnosed or treated at military treatment facilities from 1998 to 2007. RESULTS: 10,066 women were diagnosed with invasive breast cancer at DoD facilities from 1998 to 2007, of which 11.3% (1139), 23.4% (2355) and 65.2% (6572) were < 40, 40-49 and > 50 years old (yo), respectively, at diagnosis. 53% in the < 40 yo cohort were white, 25% were African American (AA) and 8% were Hispanic, with 14% undisclosed. Breast cancer in women diagnosed < 40 yo was more high grade (p < 0.0001), Stage II (p < 0.0001) and ER negative (p < 0.0001). There was a higher rate of bilateral mastectomies among the women < 40 compared to those 40-49 and > 50 (18.4% vs. 9.1% and 5.0%, respectively). Independent of disease stage, chemotherapy was given more frequently to < 40 yo (90.43%) and 40-49 yo (81.44%) than ≥ 50 yo (53.71%). The 10-year overall survival of younger women was similar to the ≥ 50 yo cohort. Outcomes in the African American and Hispanic subpopulations were comparable to the overall cohort. CONCLUSION: Younger women had a similar overall survival rate to older women despite receiving more aggressive treatment.


Assuntos
Neoplasias da Mama/epidemiologia , Mastectomia/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , United States Department of Defense/estatística & dados numéricos , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Fatores Etários , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Quimioterapia Adjuvante/estatística & dados numéricos , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricos
7.
Nano Lett ; 17(12): 7544-7551, 2017 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-29178810

RESUMO

Water vapor condensation on hydrophobic surfaces has received much attention due to its ability to rapidly shed water droplets and enhance heat transfer, anti-icing, water harvesting, energy harvesting, and self-cleaning performance. However, the mechanism of heterogeneous nucleation on hydrophobic surfaces remains poorly understood and is attributed to defects in the hydrophobic coating exposing the high surface energy substrate. Here, we observe the formation of high surface energy nanoscale agglomerates on hydrophobic coatings after condensation/evaporation cycles in ambient conditions. To investigate the deposition dynamics, we studied the nanoscale agglomerates as a function of condensation/evaporation cycles via optical and field emission scanning electron microscopy (FESEM), microgoniometric contact angle measurements, nucleation statistics, and energy dispersive X-ray spectroscopy (EDS). The FESEM and EDS results indicated that the nanoscale agglomerates stem from absorption of sulfuric acid based aerosol particles inside the droplet and adsorption of volatile organic compounds such as methanethiol (CH3SH), dimethyl disulfide (CH3SSCH), and dimethyl trisulfide (CH3SSSCH3) on the liquid-vapor interface during water vapor condensation, which act as preferential sites for heterogeneous nucleation after evaporation. The insights gained from this study elucidate fundamental aspects governing the behavior of both short- and long-term heterogeneous nucleation on hydrophobic surfaces, suggest previously unexplored microfabrication and air purification techniques, and present insights into the challenges facing the development of durable dropwise condensing surfaces.

8.
Circulation ; 132(10): 944-52, 2015 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-26169756

RESUMO

BACKGROUND: Limited penetration into the caval wall is an important securing mechanism for inferior vena cava (IVC) filters; however, caval penetration can also cause unintentional complications. The aim of this study was to assess the incidence, severity, clinical consequences, and management of filter penetration across a range of commercially available IVC filters. METHODS AND RESULTS: The MEDLINE database was searched for all studies (1970-2014) related to IVC filters. A total of 88 clinical studies and 112 case reports qualified for analysis; these studies included 9002 patients and 15 types of IVC filters. Overall, penetration was reported in 19% of patients (1699 of 9002), and 19% of those penetrations (322 of 1699) showed evidence of organ/structure involvement. Among patients with penetration, 8% were symptomatic, 45% were asymptomatic, and 47% had unknown symptomatology. The most frequently reported symptom was pain (77%, 108 of 140). Major complications were reported in 83 patients (5%). These complications required interventions including surgical removal of the IVC filter (n=63), endovascular stent placement or embolization (n=11), endovascular retrieval of the permanent filter (n=4), and percutaneous nephrostomy or ureteral stent placement (n=3). Complications led to death in 2 patients. A total of 87% of patients (127 of 146) underwent premature filter retrieval or interventions for underlying symptoms or penetration-related complications. CONCLUSIONS: Caval penetration is a frequent but clinically underrecognized complication of IVC filter placement. Symptomatic patients accounted for nearly 1/10th of all penetrations; most of these cases had organ/structure involvement. Interventions with endovascular retrieval and surgery were required in most of these symptomatic patients.


Assuntos
Remoção de Dispositivo/métodos , Gerenciamento Clínico , Filtros de Veia Cava/efeitos adversos , Veia Cava Inferior/lesões , Remoção de Dispositivo/normas , Migração de Corpo Estranho/diagnóstico , Migração de Corpo Estranho/etiologia , Humanos , Desenho de Prótese/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Veia Cava Inferior/cirurgia
9.
Am J Physiol Regul Integr Comp Physiol ; 310(7): R578-85, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26791833

RESUMO

While it is well recognized that riboflavin accumulates in breast milk as an essential vitamin for neonates, transport mechanisms for its milk excretion are not well characterized. The multidrug efflux transporter ABCG2 in the apical membrane of milk-producing mammary epithelial cells (MECs) is involved with riboflavin excretion. However, it is not clear whether MECs possess other riboflavin transport systems, which may facilitate its basolateral uptake into MECs. We report here that transcripts encoding the second (SLC52A2) and third (SLC52A3) member of the recently discovered family of SLC52A riboflavin uptake transporters are expressed in milk fat globules from human breast milk. Furthermore, Slc52a2 and Slc52a3 mRNA are upregulated in the mouse mammary gland during lactation. Importantly, the induction ofSlc52a2, which was the major Slc52a riboflavin transporter in the lactating mammary gland, was also observed at the protein level. Subcellular localization studies showed that green fluorescent protein-tagged mouse SLC52A2 mainly localized to the cell membrane, with no preferential distribution to the apical or basolateral membrane in polarized kidney MDCK cells. These results strongly implicate a potential role for SLC52A2 in riboflavin uptake by milk-producing MECs, a critical step in the transfer of riboflavin into breast milk.


Assuntos
Lactação/fisiologia , Glândulas Mamárias Animais/fisiologia , Proteínas de Membrana Transportadoras/metabolismo , Leite Humano/metabolismo , Riboflavina/metabolismo , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Regulação para Cima/fisiologia
10.
Am J Physiol Endocrinol Metab ; 307(7): E596-610, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25117410

RESUMO

The multidrug resistance efflux transporter ATP-binding cassette subfamily G member 2 (ABCG2) is not only overexpressed in certain drug-resistant cancers but is also highly expressed in the mammary gland during lactation, carrying xenobiotics and nutrients into milk. We sought to investigate the molecular mechanisms involved in the upregulation of ABCG2 during lactation. Expression profiling of different mouse Abcg2 mRNA isoforms (E1a, E1b, and E1c) revealed that E1b is predominantly expressed and induced in the lactating mouse mammary gland. Despite this induction, analyses of CpG methylation status and published ChIP-seq datasets reveal that E1b promoter sequences in the virgin gland are already hypomethylated and marked with the open chromatin histone mark H3K4me2. Using a forced-weaning model to shut down lactation, we found that within 24 h there was a significant reduction in Abcg2 mRNA expression and a loss of signal transducer and activator of transcription-5 (STAT5) occupancy at the mouse Abcg2 gene. Luciferase reporter assays further showed that some of these STAT5-binding regions that contained interferon-γ-activated sequence (GAS) motifs function as an enhancer after prolactin treatment. We conclude that Abcg2 is already poised for expression in the virgin mammary gland and that STAT5 plays an important role in Abcg2 expression during lactation.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Epigênese Genética , Células Epiteliais/metabolismo , Lactação/genética , Glândulas Mamárias Animais/metabolismo , Isoformas de RNA/genética , RNA Mensageiro/genética , Fator de Transcrição STAT5/fisiologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Ilhas de CpG , Metilação de DNA , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Regiões Promotoras Genéticas , Transdução de Sinais , Regulação para Cima
11.
J Urol ; 191(2): 427-32, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24018235

RESUMO

PURPOSE: The high costs of fertility care may deter couples from seeking care. Urologists often are asked about the costs of these treatments. To our knowledge previous studies have not addressed the direct out-of-pocket costs to couples. We characterized these expenses in patients seeking fertility care. MATERIALS AND METHODS: Couples were prospectively recruited from 8 community and academic reproductive endocrinology clinics. Each participating couple completed face-to-face or telephone interviews and cost diaries at study enrollment, and 4, 10 and 18 months of care. We determined overall out-of-pocket costs, in addition to relationships between out-of-pocket costs and treatment type, clinical outcomes and socioeconomic characteristics on multivariate linear regression analysis. RESULTS: A total of 332 couples completed cost diaries and had data available on treatment and outcomes. Average age was 36.8 and 35.6 years in men and women, respectively. Of this cohort 19% received noncycle based therapy, 4% used ovulation induction medication only, 22% underwent intrauterine insemination and 55% underwent in vitro fertilization. The median overall out-of-pocket expense was $5,338 (IQR 1,197-19,840). Couples using medication only had the lowest median out-of-pocket expenses at $912 while those using in vitro fertilization had the highest at $19,234. After multivariate adjustment the out-of-pocket expense was not significantly associated with successful pregnancy. On multivariate analysis couples treated with in vitro fertilization spent an average of $15,435 more than those treated with intrauterine insemination. Couples spent about $6,955 for each additional in vitro fertilization cycle. CONCLUSIONS: These data provide real-world estimates of out-of-pocket costs, which can be used to help couples plan for expenses that they may incur with treatment.


Assuntos
Efeitos Psicossociais da Doença , Honorários e Preços , Infertilidade/economia , Infertilidade/terapia , Técnicas de Reprodução Assistida/economia , Adulto , Estudos de Coortes , Custos e Análise de Custo , Feminino , Fertilização in vitro/economia , Humanos , Infertilidade Feminina/economia , Infertilidade Feminina/terapia , Infertilidade Masculina/economia , Infertilidade Masculina/terapia , Cobertura do Seguro/estatística & dados numéricos , Masculino , Análise Multivariada , Gravidez , Resultado da Gravidez , Fatores Socioeconômicos
12.
J Vasc Surg ; 59(1): 255-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24080132

RESUMO

BACKGROUND: Iatrogenic migration of inferior vena cava (IVC) filters is a potentially life-threatening complication that can arise during blind insertion of central venous catheters when the guide wire becomes entangled with the filter. In this study, we reviewed the occurrence of iatrogenic migration of IVC filters in the literature and assessed methods for preventing this complication. METHODS: A literature search was conducted to identify reports of filter/wire entrapment and subsequent IVC filter migration. Clinical outcomes and complications were identified. RESULTS: A total of 38 cases of filter/wire entrapment were identified. All of these cases involved J-tip guide wires. Filters included 23 Greenfield filters, 14 VenaTech filters, and one TrapEase filter. In 18 cases of filter/wire entrapment, there was migration of the filter to the heart and other central venous structures. Retrieval of the migrated filter was successful in only four of the 18 cases, and all of these cases were complicated by strut fracture and distant embolization of fragments. One patient required resuscitation during retrieval. Successful disengagement was possible in 20 cases without filter migration. CONCLUSIONS: Iatrogenic migration of an IVC filter is an uncommon complication related to wire/filter entrapment. This complication can be prevented with knowledge of the patient's history, use of proper techniques when placing a central venous catheter, identification of wire entrapment at an early stage, and use of an appropriate technique to disengage an entrapped wire.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/instrumentação , Cateteres Venosos Centrais/efeitos adversos , Migração de Corpo Estranho/prevenção & controle , Doença Iatrogênica , Filtros de Veia Cava/efeitos adversos , Remoção de Dispositivo , Desenho de Equipamento , Migração de Corpo Estranho/diagnóstico por imagem , Migração de Corpo Estranho/etiologia , Migração de Corpo Estranho/cirurgia , Humanos , Desenho de Prótese , Radiografia , Fatores de Risco , Resultado do Tratamento
13.
J Vasc Interv Radiol ; 25(6): 941-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24656176

RESUMO

PURPOSE: To investigate the prevalence and clinical sequelae of G2 filter (Bard Peripheral Vascular, Tempe, Arizona) fractures and fragment migration. MATERIALS AND METHODS: Patients who underwent G2 filter placement between October 2005 and February 2010 were assessed for filter fractures and complications. Fracture prevalence was estimated at various time points based on data from patients with known fracture status. RESULTS: Among 829 patients who underwent G2 filter placement, 684 had follow-up imaging and qualified for the study (381 men and 303 women; average age, 60.3 y; range, 15.8-95.2 y). For 541 (79%) patients, at least one image was available that contained the filter (imaging follow-up interval, 14.9 mo ± 20.0; range, 0-78.6 mo); images that did not include the filter but may have shown the migrated fracture fragment were available for 143 (21%) patients (follow-up interval, 11.2 mo ± 19.3; range, 0-83.4 mo). There were 16 fractured limbs identified in 13 patients (incidence, 1.9%; follow-up interval, 30.4 mo ± 18.7; range, 5.5-76.5 mo). Fracture fragments were identified in the pulmonary arteries (n = 4), right ventricle (n = 2), pericardium (n = 1), iliac vein (n = 1), and kidney (n = 1). Four fracture limbs remained near the filter; the remaining three could not be located. All patients with filter fracture were asymptomatic. The estimated 5-year fracture prevalence was 38% (95% confidence interval, 22.9%, 54.8%). CONCLUSIONS: The early occurrence of G2 filter fractures was low, but the incidence increased over time. No life-threatening events occurred in patients with filter fracture during the study time frame.


Assuntos
Migração de Corpo Estranho/epidemiologia , Falha de Prótese , Implantação de Prótese/instrumentação , Filtros de Veia Cava , Veia Cava Inferior , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Migração de Corpo Estranho/diagnóstico por imagem , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ohio/epidemiologia , Flebografia/métodos , Prevalência , Desenho de Prótese , Implantação de Prótese/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Veia Cava Inferior/diagnóstico por imagem , Adulto Jovem
14.
Biofouling ; 30(9): 1045-54, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25329518

RESUMO

The dynamic relationship between the settlement behaviour of marine biota (cells, spores, larvae) and the longevity of an entrapped air layer (plastron) on submersed superhydrophobic surfaces was systematically investigated. Plastron lifetime decreased with increasing hydrophobic polymer loadings, and was correlated with the settlement rate of a range of fouling species of varying length scale, motility and hydrophobic/hydrophilic surface preference. The results show that the level of fouling on immersed superhydrophobic surfaces was greater when plastron lifetimes were minimal, regardless of the length scale, motility and the surface preference of the organisms. This is the first direct demonstration of the broad-spectrum attachment-inhibiting properties of a plastron on an immersed superhydrophobic surface.


Assuntos
Incrustação Biológica/prevenção & controle , Briozoários/fisiologia , Crustáceos/fisiologia , Diatomáceas/fisiologia , Animais , Interações Hidrofóbicas e Hidrofílicas , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Polímeros/química , Propriedades de Superfície
15.
Eur J Case Rep Intern Med ; 11(6): 004491, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846664

RESUMO

Positron emission tomography (PET) has gained widespread acceptance as a valuable diagnostic tool for cancer. It is rare for a PET/CT scan to overlook the presence of metastatic disease. Sebaceous carcinoma is an uncommon malignant tumour that typically originates in the skin of the eyelid. In this case report, we present a unique case involving a metastatic sebaceous carcinoma that was not initially detected by a PET/CT scan in an 88-year-old female. Therefore, clinicians must maintain a heightened awareness of sebaceous carcinoma and exercise caution when making decisions solely based on PET scan results. It is crucial to recognise this potential limitation of PET scans in sebaceous carcinoma and consider further diagnostic approaches to ensure timely and accurate detection of sebaceous carcinoma. LEARNING POINTS: PET scans may miss slow-growing tumours such as sebaceous carcinoma.A high index of suspicion for sebaceous carcinoma is crucial, even with negative PET scans. Additional diagnostic approaches might be necessary for accurate detection.Sebaceous carcinoma is a rare but aggressive cancer. Diagnosis can be challenging due to its varied presentations.

16.
bioRxiv ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38559102

RESUMO

Mucosal healing is associated with better clinical outcomes in patients with inflammatory bowel diseases (IBDs). Unresolved injury and inflammation, on the other hand, increases pathological fibrosis and the predisposition to cancer. Loss of Smad4, a tumor suppressor, is known to increase colitis-associated cancer in mouse models of chronic IBD. Since common biological processes are involved in both injury repair and tumor growth, we sought to investigate the effect of Smad4 loss on the response to epithelial injury. To this end, Smad4 was knocked out specifically in the intestinal epithelium and transcriptomic and morphological changes compared between wild type mice and Smad4 knock out mice after DSS-induced injury. We find that Smad4 loss alleviates pathological fibrosis and enhances mucosal repair. The transcriptomic changes specific to epithelium indicate molecular changes that affect epithelial extracellular matrix (ECM) and promote enhanced mucosal repair. These findings suggest that the biological processes that promote wound healing alleviate the pathological fibrotic response to DSS. Therefore, these mucosal repair processes could be exploited to develop therapies that promote normal wound healing and prevent fibrosis. NEW AND NOTEWORTHY: We show that transcriptomic changes due to Smad4 loss in the colonic epithelium alleviates the pathological fibrotic response to DSS in an IBD mouse model of acute inflammation. Most notably, we find that collagen deposition in the epithelial ECM, as opposed to that in the lamina propria, correlates with epithelial changes that enhance wound healing. This is the first report on a mouse model providing alleviated fibrotic response in a DSS-IBD mouse model in vivo .

17.
Mol Cancer Ther ; 23(5): 606-618, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38354417

RESUMO

In recent years, the field of antibody drug conjugates (ADC) has seen a resurgence, largely driven by the clinical benefit observed in patients treated with ADCs incorporating camptothecin-based topoisomerase I inhibitor payloads. Herein, we present the development of a novel camptothecin ZD06519 (FD1), which has been specifically designed for its application as an ADC payload. A panel of camptothecin analogs with different substituents at the C-7 and C-10 positions of the camptothecin core was prepared and tested in vitro. Selected compounds spanning a range of potency and hydrophilicity were elaborated into drug-linkers, conjugated to trastuzumab, and evaluated in vitro and in vivo. ZD06519 was selected on the basis of its favorable properties as a free molecule and as an antibody conjugate, which include moderate free payload potency (∼1 nmol/L), low hydrophobicity, strong bystander activity, robust plasma stability, and high-monomeric ADC content. When conjugated to different antibodies using a clinically validated MC-GGFG-based linker, ZD06519 demonstrated impressive efficacy in multiple cell line-derived xenograft models and noteworthy tolerability in healthy mice, rats, and non-human primates.


Assuntos
Camptotecina , Imunoconjugados , Ensaios Antitumorais Modelo de Xenoenxerto , Camptotecina/farmacologia , Camptotecina/química , Imunoconjugados/farmacologia , Imunoconjugados/química , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Desenho de Fármacos , Feminino , Ratos
18.
Mol Pharmacol ; 83(2): 377-88, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23150485

RESUMO

The multidrug transporter, breast cancer resistance protein, ABCG2, is up-regulated in certain chemoresistant cancer cells and in the mammary gland during lactation. We investigated the role of the lactogenic hormone prolactin (PRL) in the regulation of ABCG2. PRL dose-dependently induced ABCG2 expression in T-47D human breast cancer cells. This induction was significantly reduced by short-interfering RNA-mediated knockdown of Janus kinase 2 (JAK2). Knockdown or pharmacologic inhibition of the down-stream signal transducer and activator of transcription-5 (STAT5) also blunted the induction of ABCG2 by PRL, suggesting a role for the JAK2/STAT5 pathway in PRL-induced ABCG2 expression. Corroborating these findings, we observed PRL-stimulated STAT5 recruitment to a region containing a putative γ-interferon activation sequence (GAS) element at -434 base pairs upstream of the ABCG2 transcription start site. Introduction of a single mutation to the -434 GAS element significantly attenuated PRL-stimulated activity of a luciferase reporter driven by the ABCG2 gene promoter and 5'-flanking region containing the -434 GAS motif. In addition, this GAS element showed strong copy number dependency in its response to PRL treatment. Interestingly, inhibitors against the mitogen-activated protein kinase and phosphoinositide-3-kinase signaling pathways significantly decreased the induction of ABCG2 by PRL without altering STAT5 recruitment to the GAS element. We conclude that the JAK2/STAT5 pathway is required but not sufficient for the induction of ABCG2 by PRL.


Assuntos
Transportadores de Cassetes de Ligação de ATP/biossíntese , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Proteínas de Neoplasias/biossíntese , Prolactina/farmacologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos , Feminino , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Células MCF-7 , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mutação/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Regiões Promotoras Genéticas/efeitos dos fármacos , RNA Mensageiro/genética , Fator de Transcrição STAT5/genética , Fator de Transcrição STAT5/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transcrição Gênica/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos
19.
Anal Bioanal Chem ; 405(28): 8969-80, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23842899

RESUMO

Two highly branched glucose polymers with similar structures--starch and glycogen--have important relations to human health. Slowly digestible and resistant starches have desirable health benefits, including the prevention and alleviation of metabolic diseases and prevention of colon cancer. Glycogen is important in regulating the use of glucose in the body, and diabetic subjects have an anomaly in their glycogen structure compared with that in healthy subjects. This paper reviews the biosynthesis-structure-property relations of these polymers, showing that polymer characterization produces knowledge which can be useful in producing healthier foods and new drug targets aimed at improving glucose storage in diabetic patients. Examples include mathematical modeling to design starch with better nutritional values, the effects of amylose fine structures on starch digestibility, the structure of slowly digested starch collected from in vitro and in vivo digestion, and the mechanism of the formation of glycogen α particles from ß particles in healthy subjects. A new method to overcome a current problem in the structural characterization of these polymers using field-flow fractionation is also given, through a technique to calibrate evaporative light scattering detection with starch.


Assuntos
Glicogênio/química , Amido/química , Alimentos Orgânicos/análise , Glucose/análise , Glicogênio/metabolismo , Humanos , Amido/metabolismo
20.
Funct Plant Biol ; 50(6): 435-454, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37105931

RESUMO

Grain yield improvement in globally important staple crops is critical in the coming decades if production is to keep pace with growing demand; so there is increasing interest in understanding and manipulating plant growth and developmental traits for better crop productivity. However, this is confounded by complex cross-scale feedback regulations and a limited ability to evaluate the consequences of manipulation on crop production. Plant/crop modelling could hold the key to deepening our understanding of dynamic trait-crop-environment interactions and predictive capabilities for supporting genetic manipulation. Using photosynthesis and crop growth as an example, this review summarises past and present experimental and modelling work, bringing about a model-guided crop improvement thrust, encompassing research into: (1) advancing cross-scale plant/crop modelling that connects across biological scales of organisation using a trait dissection-integration modelling principle; (2) improving the reliability of predicted molecular-trait-crop-environment system dynamics with experimental validation; and (3) innovative model application in synergy with cross-scale experimentation to evaluate G×M×E and predict yield outcomes of genetic intervention (or lack of it) for strategising further molecular and breeding efforts. The possible future roles of cross-scale plant/crop modelling in maximising crop improvement are discussed.


Assuntos
Produtos Agrícolas , Melhoramento Vegetal , Reprodutibilidade dos Testes , Produtos Agrícolas/genética , Grão Comestível , Fotossíntese
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