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1.
Development ; 150(21)2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37823342

RESUMO

Many developmental processes associated with fruit development occur at the floral meristem (FM). Age-regulated microRNA156 (miR156) and gibberellins (GAs) interact to control flowering time, but their interplay in subsequent stages of reproductive development is poorly understood. Here, in tomato (Solanum lycopersicum), we show that GA and miR156-targeted SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE (SPL or SBP) genes interact in the tomato FM and ovary patterning. High GA responses or overexpression of miR156 (156OE), which leads to low expression levels of miR156-silenced SBP genes, resulted in enlarged FMs, ovary indeterminacy and fruits with increased locule number. Conversely, low GA responses reduced indeterminacy and locule number, and overexpression of a S. lycopersicum (Sl)SBP15 allele that is miR156 resistant (rSBP15) reduced FM size and locule number. GA responses were partially required for the defects observed in 156OE and rSBP15 fruits. Transcriptome analysis and genetic interactions revealed shared and divergent functions of miR156-targeted SlSBP genes, PROCERA/DELLA and the classical WUSCHEL/CLAVATA pathway, which has been previously associated with meristem size and determinacy. Our findings reveal that the miR156/SlSBP/GA regulatory module is deployed differently depending on developmental stage and create novel opportunities to fine-tune aspects of fruit development that have been important for tomato domestication.


Assuntos
MicroRNAs , Solanum lycopersicum , Giberelinas/metabolismo , Solanum lycopersicum/genética , Flores , Meristema/metabolismo , Ovário/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Plantas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo
2.
Eur J Haematol ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38988123

RESUMO

OBJECTIVES: Common Variable Immunodeficiency Disorders (CVID) and Large Granular Lymphocytes leukemia (LGLL) exhibit diverse clinical manifestations including infections, dysimmunity, and lymphoproliferation. Recent decades have seen the discovery of new genes in the lymphopoiesis pathway, such as JAK-STAT. This case series supplemented by a literature review aims to describe clinical and biological characteristics of patients with both CIVD and LGLL. METHODOLOGY: Patients were included through a call for comments to French and Belgian centers and through a literature review via PubMed. Clinical characteristics were compared to two large French cohort involving CVID and LGLL patients. RESULTS: Twelve patients were included. In all cases, CVID precedes LLGL (median diagnosis delay for LLGL was 7 years). Most cases presented with splenomegaly and autoimmune cytopenia. Ten out of 12 patients underwent splenectomy during follow up. CONCLUSIONS: Patients with LGLL and CVID differ from patients without immune deficiency in term of clinical presentation and prognosis. We suggest CVID may act as a trigger of LGL lymphocytosis, due to endogenous and exogenous antigenic pressure leading to the selection of a dominant LGL clone and stimulation of the JAK-STAT pathway. The role of splenomegaly and splenectomy in LGLL onset warrant further investigation in future studies.

3.
Plant J ; 109(2): 402-414, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34882870

RESUMO

Global agriculture is dominated by a handful of species that currently supply a huge proportion of our food and feed. It additionally faces the massive challenge of providing food for 10 billion people by 2050, despite increasing environmental deterioration. One way to better plan production in the face of current and continuing climate change is to better understand how our domestication of these crops included their adaptation to environments that were highly distinct from those of their centre of origin. There are many prominent examples of this, including the development of temperate Zea mays (maize) and the alteration of day-length requirements in Solanum tuberosum (potato). Despite the pre-eminence of some 15 crops, more than 50 000 species are edible, with 7000 of these considered semi-cultivated. Opportunities afforded by next-generation sequencing technologies alongside other methods, including metabolomics and high-throughput phenotyping, are starting to contribute to a better characterization of a handful of these species. Moreover, the first examples of de novo domestication have appeared, whereby key target genes are modified in a wild species in order to confer predictable traits of agronomic value. Here, we review the scale of the challenge, drawing extensively on the characterization of past agriculture to suggest informed strategies upon which the breeding of future climate-resilient crops can be based.


Assuntos
Adaptação Fisiológica , Mudança Climática , Produtos Agrícolas/genética , Abastecimento de Alimentos , Agricultura , Produtos Agrícolas/fisiologia , Domesticação , Edição de Genes , Melhoramento Vegetal , Incerteza
4.
Plant Physiol ; 190(1): 113-126, 2022 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-35639975

RESUMO

Heterobaric leaves have bundle sheath extensions (BSEs) that compartmentalize the parenchyma, whereas homobaric leaves do not. The presence of BSEs affects leaf hydraulics and photosynthetic rate. The tomato (Solanum lycopersicum) obscuravenosa (obv) mutant lacks BSEs. Here, we identify the obv gene and the causative mutation, a nonsynonymous amino acid change that disrupts a C2H2 zinc finger motif in a putative transcription factor. This mutation exists as a polymorphism in the natural range of wild tomatoes but has increased in frequency in domesticated tomatoes, suggesting that the latter diversified into heterobaric and homobaric leaf types. The obv mutant displays reduced vein density, leaf hydraulic conductance and photosynthetic assimilation rate. We show that these and other pleiotropic effects on plant development, including changes in leaf insertion angle, leaf margin serration, minor vein density, and fruit shape, are controlled by OBV via changes in auxin signaling. Loss of function of the transcriptional regulator AUXIN RESPONSE FACTOR 4 (ARF4) also results in defective BSE development, revealing an additional component of a genetic module controlling aspects of leaf development important for ecological adaptation and subject to breeding selection.


Assuntos
Solanum lycopersicum , Ácidos Indolacéticos/metabolismo , Solanum lycopersicum/metabolismo , Fotossíntese/genética , Melhoramento Vegetal , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo
5.
J Exp Bot ; 74(20): 6349-6368, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37157899

RESUMO

S-Nitrosoglutathione plays a central role in nitric oxide (NO) homeostasis, and S-nitrosoglutathione reductase (GSNOR) regulates the cellular levels of S-nitrosoglutathione across kingdoms. Here, we investigated the role of endogenous NO in shaping shoot architecture and controlling fruit set and growth in tomato (Solanum lycopersicum). SlGSNOR silencing promoted shoot side branching and led to reduced fruit size, negatively impacting fruit yield. Greatly intensified in slgsnor knockout plants, these phenotypical changes were virtually unaffected by SlGSNOR overexpression. Silencing or knocking out of SlGSNOR intensified protein tyrosine nitration and S-nitrosation and led to aberrant auxin production and signaling in leaf primordia and fruit-setting ovaries, besides restricting the shoot basipetal polar auxin transport stream. SlGSNOR deficiency triggered extensive transcriptional reprogramming at early fruit development, reducing pericarp cell proliferation due to restrictions on auxin, gibberellin, and cytokinin production and signaling. Abnormal chloroplast development and carbon metabolism were also detected in early-developing NO-overaccumulating fruits, possibly limiting energy supply and building blocks for fruit growth. These findings provide new insights into the mechanisms by which endogenous NO fine-tunes the delicate hormonal network controlling shoot architecture, fruit set, and post-anthesis fruit development, emphasizing the relevance of NO-auxin interaction for plant development and productivity.


Assuntos
Reguladores de Crescimento de Plantas , Solanum lycopersicum , Reguladores de Crescimento de Plantas/metabolismo , Oxirredutases/metabolismo , Solanum lycopersicum/genética , Frutas/metabolismo , S-Nitrosoglutationa/metabolismo , Ácidos Indolacéticos/metabolismo , Homeostase , Óxido Nítrico/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
6.
Cardiol Young ; 33(10): 1840-1845, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36259096

RESUMO

BACKGROUND: Right ventricular outflow tract intervention spans transcatheter, surgical, or hybrid pulmonary valve replacement methodologies. Standardised pre-procedure workup includes cardiac MRI to identify an intended valve site (landing zone). Our institutional practice includes measurement of the right ventricular outflow tract perimeter (circumference) of this site in end-systole. Our primary aim was to compare patients by their perimeter values to the palliative interventions performed (transcatheter versus surgical/hybrid methodologies). METHODS: Retrospective review of patients undergoing pulmonary valve replacement from January 2017 to 2021. We performed perimeter measurements at the intended valve site on advanced imaging; the outcomes of interventions were outlined via descriptive and statistical analyses. RESULTS: A total of 37 patients underwent pulmonary valve replacement that met study criteria - 21 transcatheter, 7 surgical, and 9 hybrid. Median age at intervention was 26 years (range 8-70). The mean end-systolic perimeter of the transcatheter cohort was 88.9 ± 8.7 mm and in the surgical/hybrid cohort measured 106.6 ± 7.5 mm. For the transcatheter cohort, the median "circularised" diameter derived from the perimeter measurement (divided by π) was 27.7 mm (range 24.3-32.4). Notably, this correlated (r = 0.93, p < 0.01) with the median diameter of the narrowest region during actual transcatheter right ventricular outflow tract balloon sizing (lateral imaging) of 27.1 mm (range 23.2-30.1). CONCLUSIONS: Right ventricular outflow tract perimeter measurement to determine circularised diameter is useful in planning pulmonary valve replacement in terms of candidacy of transcatheter versus the need for a surgical/hybrid approach. The circularised diameter correlates with transcatheter right ventricular outflow tract balloon sizing.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Insuficiência da Valva Pulmonar , Valva Pulmonar , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Valva Pulmonar/diagnóstico por imagem , Valva Pulmonar/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Resultado do Tratamento , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/cirurgia , Estudos Retrospectivos , Cateterismo Cardíaco/métodos
7.
Plant Cell Physiol ; 63(1): 120-134, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-34665867

RESUMO

The bZIP transcription factor (TF) SlTGA2.2 was previously highlighted as a possible hub in a network regulating fruit growth and transition to ripening (maturation phase). It belongs to a clade of TFs well known for their involvement in the regulation of the salicylic acid-dependent systemic acquired resistance. To investigate if this TGA TF plays a role in tomato fruit growth and maturation, we took advantage of the fruit-specific SlPPC2 promoter (PPC2pro) to target the expression of a SlTGA2.2-SRDX chimeric repressor in a developmental window restricted to early fruit growth and maturation. Here, we show that this SlTGA2.2-SRDX repressor alters early fruit development and metabolism, including chloroplast number and structure, considerably extends the time necessary to reach the mature green stage and slows down fruit ripening. RNA sequencing and plant hormone analyses reveal that PPC2pro:SlTGA2.2-SRDX fruits are maintained in an immature stage as long as PPC2pro is active, through early modifications of plant hormonal signaling and down-regulation of MADS-RIN and NAC-NOR ripening regulators. Once PPC2pro becomes inactive and therefore SlTGA2.2-SRDX expression is reduced, ripening can proceed, albeit at a slower pace than normal. Altogether, this work emphasizes the developmental continuum between fruit growth, maturation and ripening and provides a useful tool to alter and study the molecular bases of tomato fruit transition to ripening.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Frutas/crescimento & desenvolvimento , Frutas/genética , Filogenia , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/genética , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genótipo , Mutação
8.
Br J Dermatol ; 186(3): 564-574, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34632574

RESUMO

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Síndromes Mielodisplásicas , Humanos , Inflamação/genética , Mutação/genética , Síndromes Mielodisplásicas/diagnóstico , Enzimas Ativadoras de Ubiquitina
9.
J Chem Phys ; 157(24): 244504, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36586975

RESUMO

We investigate the structural relaxation of a soft-sphere liquid quenched isochorically (ϕ = 0.7) and instantaneously to different temperatures Tf above and below the glass transition. For this, we combine extensive Brownian dynamics simulations and theoretical calculations based on the non-equilibrium self-consistent generalized Langevin equation (NE-SCGLE) theory. The response of the liquid to a quench generally consists of a sub-linear increase of the α-relaxation time with system's age. Approaching the ideal glass-transition temperature from above (Tf > Ta), sub-aging appears as a transient process describing a broad equilibration crossover for quenches to nearly arrested states. This allows us to empirically determine an equilibration timescale teq(Tf) that becomes increasingly longer as Tf approaches Ta. For quenches inside the glass (Tf ≤ Ta), the growth rate of the structural relaxation time becomes progressively larger as Tf decreases and, unlike the equilibration scenario, τα remains evolving within the whole observation time-window. These features are consistently found in theory and simulations with remarkable semi-quantitative agreement and coincide with those revealed in a previous and complementary study [P. Mendoza-Méndez et al., Phys. Rev. 96, 022608 (2017)] that considered a sequence of quenches with fixed final temperature Tf = 0 but increasing ϕ toward the hard-sphere dynamical arrest volume fraction ϕHS a=0.582. The NE-SCGLE analysis, however, unveils various fundamental aspects of the glass transition, involving the abrupt passage from the ordinary equilibration scenario to the persistent aging effects that are characteristic of glass-forming liquids. The theory also explains that, within the time window of any experimental observation, this can only be observed as a continuous crossover.


Assuntos
Vidro , Simulação de Dinâmica Molecular , Temperatura , Temperatura de Transição , Vidro/química
10.
Planta ; 254(1): 11, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34160697

RESUMO

MAIN CONCLUSION: Cultivated tomatoes harboring the plastid-derived sesquiterpenes from S. habrochaites have altered type-VI trichome morphology and unveil additional genetic components necessary for piercing-sucking pest resistance. Arthropod resistance in the tomato wild relative Solanum habrochaites LA1777 is linked to specific sesquiterpene biosynthesis. The Sesquiterpene synthase 2 (SsT2) gene cluster on LA1777 chromosome 8 controls plastid-derived sesquiterpene synthesis. The main genes at SsT2 are Z-prenyltransferase (zFPS) and Santalene and Bergamotene Synthase (SBS), which produce α-santalene, ß-bergamotene, and α-bergamotene in LA1777 round-shaped type-VI glandular trichomes. Cultivated tomatoes have mushroom-shaped type-VI trichomes with much smaller glands that contain low levels of monoterpenes and cytosolic-derived sesquiterpenes, not presenting the same pest resistance as in LA1777. We successfully transferred zFPS and SBS from LA1777 to cultivated tomato (cv. Micro-Tom, MT) by a backcrossing approach. The trichomes of the MT-Sst2 introgressed line produced high levels of the plastid-derived sesquiterpenes. The type-VI trichome internal storage-cavity size increased in MT-Sst2, probably as an effect of the increased amount of sesquiterpenes, although it was not enough to mimic the round-shaped LA1777 trichomes. The presence of high amounts of plastid-derived sesquiterpenes was also not sufficient to confer resistance to various tomato piercing-sucking pests, indicating that the effect of the sesquiterpenes found in the wild S. habrochaites can be insect specific. Our results provide for a better understanding of the morphology of S. habrochaites type-VI trichomes and paves the way to obtain insect-resistant tomatoes.


Assuntos
Artrópodes , Sesquiterpenos , Solanum lycopersicum , Solanum , Animais , Solanum lycopersicum/genética , Solanum/genética , Tricomas
11.
New Phytol ; 231(1): 365-381, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33826751

RESUMO

Moniliophthora perniciosa causes witches' broom disease of cacao and inflicts symptoms suggestive of hormonal imbalance. We investigated whether infection of the tomato (Solanum lycopersicum) model system Micro-Tom (MT) by the Solanaceae (S)-biotype of Moniliophthora perniciosa, which causes stem swelling and hypertrophic growth of axillary shoots, results from changes in host cytokinin metabolism. Inoculation of an MT-transgenic line that overexpresses the Arabidopsis CYTOKININ OXIDASE-2 gene (35S::AtCKX2) resulted in a reduction in disease incidence and stem diameter. RNA-sequencing analysis of infected MT and 35S::AtCKX2 revealed the activation of cytokinin-responsive marker genes when symptoms were conspicuous. The expression of an Moniliophthora perniciosa tRNA-ISOPENTENYL-TRANSFERASE suggests the production of isopentenyladenine (iP), detected in mycelia grown in vitro. Inoculated MT stems showed higher levels of dihydrozeatin and trans-zeatin but not iP. The application of benzyladenine induced symptoms similar to infection, whereas applying the cytokinin receptor inhibitors LGR-991 and PI55 decreased symptoms. Moniliophthora perniciosa produces iP that might contribute to cytokinin synthesis by the host, which results in vascular and cortex enlargement, axillary shoot outgrowth, reduction in root biomass and an increase in fruit locule number. This strategy may be associated with the manipulation of sink establishment to favour infection by the fungus.


Assuntos
Agaricales , Cacau , Solanum lycopersicum , Citocininas , Solanum lycopersicum/genética , Doenças por Fitoplasmas , Doenças das Plantas
12.
Cardiol Young ; 31(7): 1057-1188, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34323211

RESUMO

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.


Assuntos
Cardiopatias Congênitas , Classificação Internacional de Doenças , Criança , Feminino , Humanos , Sistema de Registros , Sociedades Médicas , Organização Mundial da Saúde
13.
Plant Cell Environ ; 43(1): 76-86, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31691316

RESUMO

A major issue in modern agriculture is water loss through stomata during photosynthetic carbon assimilation. In water-limited ecosystems, annual plants have strategies to synchronize their growth and reproduction to the availability of water. Some species or ecotypes of flowers are early to ensure that their life cycles are completed before the onset of late season terminal drought ("drought escape"). This accelerated flowering correlates with low water-use efficiency (WUE). The molecular players and physiological mechanisms involved in this coordination are not fully understood. We analyzed WUE using gravimetry, gas exchange, and carbon isotope discrimination in florigen deficient (sft mutant), wild-type (Micro-Tom), and florigen over-expressing (SFT-ox) tomato lines. Increased florigen expression led to accelerated flowering time and reduced WUE. The low WUE of SFT-ox was driven by higher stomatal conductance and thinner leaf blades. This florigen-driven effect on WUE appears be independent of abscisic acid (ABA). Our results open a new avenue to increase WUE in crops in an ABA-independent manner. Manipulation of florigen levels could allow us to produce crops with a life cycle synchronized to water availability.


Assuntos
Florígeno/metabolismo , Solanum lycopersicum/metabolismo , Água/fisiologia , Ácido Abscísico/metabolismo , Isótopos de Carbono/metabolismo , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Secas , Ecótipo , Flores/genética , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Solanum lycopersicum/genética , Fotossíntese , Desenvolvimento Vegetal , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estômatos de Plantas/genética , Estômatos de Plantas/metabolismo
14.
BMC Infect Dis ; 20(1): 850, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33198667

RESUMO

BACKGROUND: The objective of the study was to describe the evolution of chronic non-AIDS related diseases and their risk factors, in patients living with HIV (PLHIV) in the French ANRS CO3 Aquitaine prospective cohort, observed both in 2004 and in 2014 in order to improve long-term healthcare management. METHODS: The ANRS CO3 Aquitaine cohort prospectively collects epidemiological, clinical, biological and therapeutic data on PLHIV in the French Aquitaine region. Two cross sectional analyses were performed in 2004 and 2014, to investigate the patient characteristics, HIV RNA, CD4 counts and prevalence of some common comorbidities and treatment. RESULTS: 2138 PLHIV (71% male, median age 52.2 years in 2014) were identified for inclusion in the study, including participants who were registered in the cohort with at least one hospital visit recorded in both 2004 and 2014. Significant increases in the prevalence of diagnosed chronic kidney disease (CKD), bone fractures, cardiovascular events (CVE), hypertension, diabetes and dyslipidaemia, as well as an increase in treatment or prevention for these conditions (statins, clopidogrel, aspirin) were observed. It was also reflected in the increase in the proportion of patients in the "high" or "very high" risk groups of the disease risk scores for CKD, CVE and bone fracture score. CONCLUSIONS: Between 2004 and 2014, the aging PLHIV population identified in the French ANRS CO3 Aquitaine prospective cohort experienced an overall higher prevalence of non-HIV related comorbidities, including CKD and CVD. Long-term healthcare management and long-term health outcomes could be improved for PLHIV by: careful HIV management according to current recommendations with optimal selection of antiretrovirals, and early management of comorbidities through recommended lifestyle improvements and preventative measures.


Assuntos
Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Fraturas Ósseas/epidemiologia , Infecções por HIV/epidemiologia , HIV-1/genética , Hipertensão/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Adulto , Envelhecimento , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Comorbidade/tendências , Estudos Transversais , Feminino , França/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , RNA Viral/análise , Fatores de Risco
15.
New Phytol ; 221(3): 1328-1344, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30238569

RESUMO

Age-regulated microRNA156 (miR156) and targets similarly control the competence to flower in diverse species. By contrast, the diterpene hormone gibberellin (GA) and the microRNA319-regulated TEOSINTE BRANCHED/CYCLOIDEA/PCF (TCP) transcription factors promote flowering in the facultative long-day Arabidopsis thaliana, but suppress it in the day-neutral tomato (Solanum lycopersicum). We combined genetic and molecular studies and described a new interplay between GA and two unrelated miRNA-associated pathways that modulates tomato transition to flowering. Tomato PROCERA/DELLA activity is required to promote flowering along with the miR156-targeted SQUAMOSA PROMOTER BINDING-LIKE (SPL/SBP) transcription factors by activating SINGLE FLOWER TRUSS (SFT) in the leaves and the MADS-Box gene APETALA1(AP1)/MC at the shoot apex. Conversely, miR319-targeted LANCEOLATE represses floral transition by increasing GA concentrations and inactivating SFT in the leaves and AP1/MC at the shoot apex. Importantly, the combination of high GA concentrations/responses with the loss of SPL/SPB function impaired canonical meristem maturation and flower initiation in tomato. Our results reveal a cooperative regulation of tomato floral induction and flower development, integrating age cues (miR156 module) with GA responses and miR319-controlled pathways. Importantly, this study contributes to elucidate the mechanisms underlying the effects of GA in controlling flowering time in a day-neutral species.


Assuntos
Flores/crescimento & desenvolvimento , Giberelinas/metabolismo , MicroRNAs/metabolismo , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/genética , Inflorescência/crescimento & desenvolvimento , Meristema/crescimento & desenvolvimento , MicroRNAs/genética , Modelos Biológicos , Mutação/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
16.
Plant Physiol ; 176(4): 2904-2916, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29500181

RESUMO

The SELF PRUNING (SP) gene is a key regulator of growth habit in tomato (Solanum lycopersicum). It is an ortholog of TERMINAL FLOWER1, a phosphatidylethanolamine-binding protein with antiflorigenic activity in Arabidopsis (Arabidopsis thaliana). A spontaneous loss-of-function mutation (sp) has been bred into several industrial tomato cultivars, as it produces a suite of pleiotropic effects that are favorable for mechanical harvesting, including determinate growth habit, short plant stature, and simultaneous fruit ripening. However, the physiological basis for these phenotypic differences has not been thoroughly explained. Here, we show that the sp mutation alters polar auxin transport as well as auxin responses, such as gravitropic curvature and elongation of excised hypocotyl segments. We also demonstrate that free auxin levels and auxin-regulated gene expression patterns are altered in sp mutants. Furthermore, diageotropica, a mutation in a gene encoding a cyclophilin A protein, appears to confer epistatic effects with sp Our results indicate that SP affects the tomato growth habit at least in part by influencing auxin transport and responsiveness. These findings suggest potential novel targets that could be manipulated for controlling plant growth habit and improving productivity.


Assuntos
Ciclofilina A/metabolismo , Frutas/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas de Plantas/metabolismo , Solanum lycopersicum/metabolismo , Transporte Biológico , Ciclofilina A/genética , Frutas/genética , Frutas/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Ácidos Indolacéticos/farmacologia , Solanum lycopersicum/genética , Solanum lycopersicum/crescimento & desenvolvimento , Mutação , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Proteínas de Plantas/genética
17.
Plant Cell Environ ; 42(5): 1575-1589, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30523629

RESUMO

Coordination between structural and physiological traits is key to plants' responses to environmental fluctuations. In heterobaric leaves, bundle sheath extensions (BSEs) increase photosynthetic performance (light-saturated rates of photosynthesis, Amax ) and water transport capacity (leaf hydraulic conductance, Kleaf ). However, it is not clear how BSEs affect these and other leaf developmental and physiological parameters in response to environmental conditions. The obscuravenosa (obv) mutation, found in many commercial tomato varieties, leads to absence of BSEs. We examined structural and physiological traits of tomato heterobaric and homobaric (obv) near-isogenic lines grown at two different irradiance levels. Kleaf , minor vein density, and stomatal pore area index decreased with shading in heterobaric but not in homobaric leaves, which show similarly lower values in both conditions. Homobaric plants, on the other hand, showed increased Amax , leaf intercellular air spaces, and mesophyll surface area exposed to intercellular airspace (Smes ) in comparison with heterobaric plants when both were grown in the shade. BSEs further affected carbon isotope discrimination, a proxy for long-term water-use efficiency. BSEs confer plasticity in traits related to leaf structure and function in response to irradiance levels and might act as a hub integrating leaf structure, photosynthetic function, and water supply and demand.


Assuntos
Folhas de Planta , Feixe Vascular de Plantas/citologia , Feixe Vascular de Plantas/fisiologia , Luz , Solanum lycopersicum , Fotossíntese/fisiologia , Folhas de Planta/anatomia & histologia , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/fisiologia , Plantas Geneticamente Modificadas , Água/fisiologia
19.
Plant Cell Rep ; 38(5): 623-636, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30737538

RESUMO

KEY MESSAGE: Complementation of the "Micro-Tom" tomato tangerine mutant with a Citrus CRTISO allele restores the wild-type fruit carotenoid profile, indicating that the Citrus allele encodes an authentic functional carotenoid isomerase. Citrus fruits are rich in carotenoids; the genus offers a large diversity in composition, yet to be fully explored to improve fruit nutritional quality. As perennial tree species, Citrus lack the resources for functional genetic studies, requiring the use of model plant systems. Here, we used the "Micro-Tom" (MT) tomato carrying the tangerine mutation (t), deficient for the carotenoid isomerase (CRTISO) gene, to functionally characterize the homologous C. sinensis genes. We identified four putative loci in the C. sinensis genome, named CsCRTISO, CsCRTISO-Like 1, CsCRTISO-Like 2, and CsCRTISO-Like 2B, with the latter as a presumed duplication of CRTISO-Like 2. In general, all the Citrus paralogs showed less expression specialization than the tomato ones, with CsCRTISO being the most expressed gene in all tissues analyzed. MT-t plants were successfully complemented with the CsCRTISO, and fruits showed a carotenoid profile similar to the control, indicating that the Citrus allele indeed encodes an authentic functional carotenoid isomerase and that the signal peptide is functional in tomato. MT was silenced using an inverted repeat of a fragment from the Citrus CRTISO resulting in a stronger phenotype than MT-t. MT-t and MT silenced for CRTISO presented an overall decrease in transcript accumulation of all genes from the biosynthesis pathway. The expression of the Citrus CRTISO gene is able to restore the biosynthesis of carotenoids with the appropriate regulation in MT-t. The decrease in transcript accumulation in MT-t and MT-CRTISO-suppressed lines reinforces previous suggestions that transcriptional regulation of the carotenoid biosynthesis involves regulatory loops by intermediate products.


Assuntos
Carotenoides/metabolismo , Citrus/metabolismo , Frutas/metabolismo , Solanum lycopersicum/metabolismo , Citrus/genética , Frutas/genética , Regulação da Expressão Gênica de Plantas , Solanum lycopersicum/genética , Mutação
20.
J Eur Acad Dermatol Venereol ; 33(2): 405-409, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29888406

RESUMO

BACKGROUND: Survival can be threatened in certain forms of systemic sclerosis (SSc) so clear prognostic factors are needed. OBJECTIVES: The aim of this meta-analysis was to assess the association between the presence of digital ulcers (DUs) and mortality in SSc. METHODS: We performed a systematic review and meta-analysis in the Pubmed and Scopus databases from the earliest records to May 2017. Two research strategies were performed: « systemic sclerosis ¼ and « digital ulcers ¼ (strategy A); « systemic sclerosis ¼ and « mortality ¼ (strategy B). The primary outcome was the mortality associated with the presence of DUs in patients with SSc. RESULTS: The literature search identified 1473 citations. Fifty-nine studies were examined for full text. Ten articles were included for the meta-analysis. SSc patients with DUs had an increased pooled mortality risk: RR = 1.53 (IC 95%: [1.23-1.90]). CONCLUSIONS: This meta-analysis revealed a higher mortality in SSc patients with associated DUs. Having DUs may be a predictive factor of developing organ involvement such as pulmonary or cardiovascular events that could be associated with poor survival. It suggests that early screening of DUs in SSc patients is important to identify patients most at risk of poor survival.


Assuntos
Causas de Morte , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/patologia , Úlcera Cutânea/epidemiologia , Úlcera Cutânea/patologia , Comorbidade , Intervalos de Confiança , Feminino , Dedos , Humanos , Masculino , Modelos de Riscos Proporcionais , Medição de Risco , Escleroderma Sistêmico/fisiopatologia , Índice de Gravidade de Doença , Úlcera Cutânea/fisiopatologia , Análise de Sobrevida
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