RESUMEN
Arthropod herbivory poses a serious threat to crop yield, prompting plants to employ intricate defense mechanisms against pest feeding. The generalist pest 2-spotted spider mite (Tetranychus urticae) inflicts rapid damage and remains challenging due to its broad target range. In this study, we explored the Arabidopsis (Arabidopsis thaliana) response to T. urticae infestation, revealing the induction of abscisic acid (ABA), a hormone typically associated with abiotic stress adaptation, and stomatal closure during water stress. Leveraging a Forster resonance energy transfer (FRET)-based ABA biosensor (nlsABACUS2-400n), we observed elevated ABA levels in various leaf cell types postmite feeding. While ABA's role in pest resistance or susceptibility has been debated, an ABA-deficient mutant exhibited increased mite infestation alongside intact canonical biotic stress signaling, indicating an independent function of ABA in mite defense. We established that ABA-triggered stomatal closure effectively hinders mite feeding and minimizes leaf cell damage through genetic and pharmacological interventions targeting ABA levels, ABA signaling, stomatal aperture, and density. This study underscores the critical interplay between biotic and abiotic stresses in plants, highlighting how the vulnerability to mite infestation arising from open stomata, crucial for transpiration and photosynthesis, reinforces the intricate relationship between these stress types.
Asunto(s)
Ácido Abscísico , Arabidopsis , Herbivoria , Estomas de Plantas , Tetranychidae , Animales , Ácido Abscísico/metabolismo , Tetranychidae/fisiología , Estomas de Plantas/fisiología , Arabidopsis/fisiología , Arabidopsis/genética , Arabidopsis/parasitología , Transducción de Señal , Hojas de la Planta/parasitología , Hojas de la Planta/fisiología , Hojas de la Planta/metabolismoRESUMEN
BACKGROUND: Plants have acquired a repertoire of mechanisms to combat biotic stressors, which may vary depending on the feeding strategies of herbivores and the plant species. Hormonal regulation crucially modulates this malleable defense response. Jasmonic acid (JA) and salicylic acid (SA) stand out as pivotal regulators of defense, while other hormones like abscisic acid (ABA), ethylene (ET), gibberellic acid (GA) or auxin also play a role in modulating plant-pest interactions. The plant defense response has been described to elicit effects in distal tissues, whereby aboveground herbivory can influence belowground response, and vice versa. This impact on distal tissues may be contingent upon the feeding guild, even affecting both the recovery of infested tissues and those that have not suffered active infestation. RESULTS: To study how phytophagous with distinct feeding strategies may differently trigger the plant defense response during and after infestation in both infested and distal tissues, Arabidopsis thaliana L. rosettes were infested separately with the chewing herbivore Pieris brassicae L. and the piercing-sucker Tetranychus urticae Koch. Moderate infestation conditions were selected for both pests, though no quantitative control of damage levels was carried out. Feeding mode did distinctly influence the transcriptomic response of the plant under these conditions. Though overall affected processes were similar under either infestation, their magnitude differed significantly. Plants infested with P. brassicae exhibited a short-term response, involving stress-related genes, JA and ABA regulation and suppressing growth-related genes. In contrast, T. urticae elicited a longer transcriptomic response in plants, albeit with a lower degree of differential expression, in particular influencing SA regulation. These distinct defense responses transcended beyond infestation and through the roots, where hormonal response, flavonoid regulation or cell wall reorganization were differentially affected. CONCLUSION: These outcomes confirm that the existent divergent transcriptomic responses elicited by herbivores employing distinct feeding strategies possess the capacity to extend beyond infestation and even affect tissues that have not been directly infested. This remarks the importance of considering the entire plant's response to localized biotic stresses.
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Arabidopsis , Mariposas Diurnas , Animales , Transcriptoma , Herbivoria/fisiología , Masticación , Mariposas Diurnas/fisiología , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Ciclopentanos/metabolismoRESUMEN
Composite generalist herbivores are comprised of host-adapted populations that retain the ability to shift hosts. The degree and overlap of mechanisms used by host-adapted generalist and specialist herbivores to overcome the same host plant defenses are largely unknown. Tetranychidae mites are exceptionally suited to address the relationship between host adaptation and specialization in herbivores as this group harbors closely related species with remarkably different host ranges-an extreme generalist the two-spotted spider mite (Tetranychus urticae Koch [Tu]) and the Solanaceous specialist Tetranychus evansi (Te). Here, we used tomato-adapted two-spotted spider mite (Tu-A) and Te populations to compare mechanisms underlying their host adaptation and specialization. We show that both mites attenuate induced tomato defenses, including protease inhibitors (PIs) that target mite cathepsin L digestive proteases. While Te solely relies on transcriptional attenuation of PI induction, Tu and Tu-A have elevated constitutive activity of cathepsin L proteases, making them less susceptible to plant anti-digestive proteins. Tu-A and Te also rely on detoxification of tomato constitutive defenses. Te uses esterase and P450 activities, while Tu-A depends on the activity of all major detoxification enzymatic classes to disarm tomato defensive compounds to a lesser extent. Thus, even though both Tu-A and Te use similar mechanisms to counteract tomato defenses, Te can better cope with them. This finding is congruent with the ecological and evolutionary times required to establish mite adaptation and specialization states, respectively.
Asunto(s)
Tetranychidae , Animales , Adaptación al Huésped , Catepsina L , Plantas , Evolución Biológica , HerbivoriaRESUMEN
Topicals and chemical peels are the standard of care for management of facial hyperpigmentation. However, traditional therapies have come under recent scrutiny, such as topical hydroquinone (HQ) has some regulatory restrictions, and high concentration trichloroacetic acid (TCA) peel pose a risk in patients with skin of colour. The objective of our research was to identify, investigate and elucidate the mechanism of action of a novel TCA- and HQ-free professional-use chemical peel to manage common types of facial hyperpigmentation. Using computational modelling and in vitro assays on tyrosinase, we identified proprietary multi-acid synergistic technology (MAST). After a single application on human skin explants, MAST peel was found to be more effective than a commercial HQ peel in inhibiting melanin (histochemical imaging and gene expression). All participants completed the case study (N = 9) without any adverse events. After administration of the MAST peel by a dermatologist, the scoring and VISIA photography reported improvements in hyperpigmentation, texture and erythema, which could be linked to underlying pathophysiological changes in skin after peeling, visualized by non-invasive optical biopsy of face. Using reflectance confocal microscopy (VivaScope®) and multiphoton tomography (MPTflex™), we observed reduction in melanin, increase in metabolic activity of keratinocytes, and no signs of inflammatory cells after peeling. Subsequent swabbing of the cheek skin found no microbiota dysbiosis resulting from the chemical peel. The strong efficacy with minimum downtime and no adverse events could be linked to the synergistic action of the ingredients in the novel HQ- and TCA-free professional peel technology.
Asunto(s)
Hidroquinonas , Hiperpigmentación , Melaninas , Humanos , Hiperpigmentación/tratamiento farmacológico , Piel , Biología Computacional , BiopsiaRESUMEN
OBJECTIVE: Analyze fecal and blood samples at point of diagnosis in IgE mediated cow's milk protein allergy (CMPA) and non-IgE mediated (NIM)-CMPA patients to look for potential new biomarkers. PATIENTS AND METHODS: Fourteen patients with IgE mediated CMPA and 13 with NIM-CMPA were recruited in three hospitals in the north of Spain, and were compared with 25 infants from a control group of the same age range. To characterize intestinal microbiota, 16S rDNA gene and internal transcribed spacer amplicons of bifidobacteria were sequenced with Illumina technology. Fatty acids were analyzed by gas chromatography, meanwhile intestinal inflammation markers were quantified by enzyme-linked immunosorbent assay and a multiplex system. Immunological analysis of blood was performed by flow cytometry. RESULTS: The fecal results obtained in the NIM-CMPA group stand out. Among them, a significant reduction in the abundance of Bifidobacteriaceae and Bifidobacterium sequences with respect to controls was observed. Bifidobacterial species were also different, highlighting the lower abundance of Bifidobacterium breve sequences. Fecal calprotectin levels were found to be significantly elevated in relation to IgE mediated patients. Also, a higher excretion of IL-10 and a lower excretion of IL-1ra and platelet derived growth factor-BB was found in NIM-CMPA patients. CONCLUSIONS: The differential fecal parameters found in NIM-CMPA patients could be useful in the diagnosis of NIM food allergy to CM proteins.
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Hipersensibilidad a los Alimentos , Microbioma Gastrointestinal , Hipersensibilidad a la Leche , Lactante , Femenino , Animales , Humanos , Bovinos , Inmunoglobulina E , Hipersensibilidad a la Leche/diagnóstico , Proteínas de la LecheRESUMEN
OBJECTIVE: Periorbital skin ageing signs are multidimensional, highly visible and a concern for many. We evaluated the potential efficacy of an eye cream to diminish these signs. METHODS: Biological markers associated with ageing, barrier function and homeostasis were analysed in vitro to determine the effects of topically applied eye cream, compared to those of a placebo using human skin tissue models and/or explants. Collagen IV, elastin and bone morphogenic protein 4 (BMP4) expression was investigated by immunohistochemical labelling, while filaggrin, kallikrein 7 (KLK7) and HB-EGF were evaluated by RT-qPCR. IL-1α and melanin levels in darkly pigmented skin models were also quantified. The protective effect of the cream on glycation was assessed by a non-enzymatic assay. Finally, the benefits of twice-daily applications of the eye cream for 56 days were instrumentally and clinically evaluated on 33 women. RESULTS: Only the eye cream, not the placebo, stimulated collagen IV and BMP4 protein expression, as well as increased elastin fibre length. It also led to higher HB-EGF, filaggrin and KLK7 mRNA levels. The placebo and the eye cream did not induce changes in IL-1α and melanin levels, but both reduced non-enzymatic glycation. When assessing the in vivo effects of the cream, short-term results indicated skin hydration, transepidermal water loss (TEWL) and skin profilometry improvement within 15 min. Instrumental evaluations of wrinkles showed a reduction after 7 days, which was clinically perceivable after 28 or 56 days. The eye-opening angle and eyelid sagging also improved after seven and 28 days, respectively. Finally, dark circles became lighter within 7 days (instrumental measurement) or 28 days (clinical assessment). CONCLUSION: The instrumental and clinical evaluations revealed that the eye cream reduced all periorbital ageing signs evaluated. Its effects are supported by the in vitro and ex vivo analyses of molecular markers.
OBJECTIF: Les signes de vieillissement de la peau périorbitaire sont nombreux, très visibles et préoccupent de nombreuses personnes. Nous avons évalué l'efficacité potentielle d'une crème pour les yeux pour atténuer ces signes. MÉTHODES: Les marqueurs biologiques associés au vieillissement, à la fonction barrière et à l'homéostasie de la peau ont été analysés in vitro pour évaluer l'efficacité d'une crème pour les yeux appliquée localement. Ces effets ont été comparés à ceux d'un placebo, sur des modèles et/ou des explants de tissus cutanés humains. L'expression du collagène IV, de l'élastine et de la protéine morphogénique osseuse 4 (BMP4) a été étudiée par marquage immunohistochimique. Celle de la filaggrine, de la kallikréine 7 (KLK7), et du HBEGF par RTqPCR. Les niveaux d'IL1α et de mélanine dans un modèle de peau pigmentée ont également été quantifiés. L'effet protecteur de la crème sur la glycation a été évalué par un test non enzymatique. Enfin, les bénéfices d'une application biquotidienne de la crème pour les yeux ont été évalués instrumentalement et cliniquement sur 33 femmes pendant 56 jours. RÉSULTATS: Seule la crème pour les yeux a stimulé l'expression du collagène IV et de BMP4 en comparaison avec le placebo. La crème est aussi la seule à augmenter la longueur des fibres d'élastine. Elle a également entraîné une augmentation des niveaux d'ARNm de HBEGF, de la filaggrine et de KLK7. Le placebo et la crème pour les yeux n'ont pas modifié les niveaux d'IL1α et de la mélanine, mais ont tous deux réduit la glycation non enzymatique. Lors de l'évaluation des effets in vivo, les résultats à court terme ont montré une amélioration de l'hydratation de la peau, de la Perte Insensible en Eau (PIE) et du profil de la peau en 15 min. Les évaluations instrumentales de la profondeur des rides ont indiqué une réduction après 7 jours d'application, réduction cliniquement perceptible après 28 ou 56 jours. La crème périorbitale induit également une amélioration de l'angle d'ouverture des yeux et de l'affaissement des paupières respectivement après 7 et 28 jours. Enfin, les cernes sont devenus plus clairs après 7 jours (mesure instrumentale) ou 28 jours (évaluation clinique). CONCLUSION: Les évaluations instrumentales et cliniques ont révélé que la crème pour les yeux réduisait tous les signes de vieillissement périorbitaires évalués. Ses effets sont confirmés par les analyses in vitro et ex vivo des marqueurs moléculaires.
RESUMEN
Plant-pest interactions involve multifaceted processes encompassing a complex crosstalk of pathways, molecules, and regulators aimed at overcoming defenses developed by each interacting organism. Among plant defensive compounds against phytophagous arthropods, cyanide-derived products are toxic molecules that directly target pest physiology. Here, we identified the Arabidopsis (Arabidopsis thaliana) gene encoding hydroxynitrile lyase (AtHNL, At5g10300) as one gene induced in response to spider mite (Tetranychus urticae) infestation. AtHNL catalyzes the reversible interconversion between cyanohydrins and derived carbonyl compounds with free cyanide. AtHNL loss- and gain-of-function Arabidopsis plants showed that specific activity of AtHNL using mandelonitrile as substrate was higher in the overexpressing lines than in wild-type (WT) and mutant lines. Concomitantly, mandelonitrile accumulated at higher levels in mutant lines than in WT plants and was significantly reduced in the AtHNL overexpressing lines. After mite infestation, mandelonitrile content increased in WT and overexpressing plants but not in mutant lines, while hydrogen cyanide (HCN) accumulated in the three infested Arabidopsis genotypes. Feeding bioassays demonstrated that the AtHNL gene participated in Arabidopsis defense against T. urticae. The reduced leaf damage detected in the AtHNL overexpressing lines reflected the mite's reduced ability to feed on leaves, which consequently restricted mite fecundity. In turn, mites upregulated TuCAS1 encoding ß-cyanoalanine synthase to avoid the respiratory damage produced by HCN. This detoxification effect was functionally demonstrated by reduced mite fecundity observed when dsRNA-TuCAS-treated mites fed on WT plants and hnl1 mutant lines. These findings add more players in the Arabidopsis-T. urticae interplay to overcome mutual defenses.
Asunto(s)
Arabidopsis , Tetranychidae , Aldehído-Liasas/genética , Animales , Arabidopsis/genética , Cianuros , Plantas , Tetranychidae/genéticaRESUMEN
Multiple sclerosis (MS) is a highly heterogeneous demyelinating disease of the central nervous system (CNS) that needs for reliable biomarkers to foresee disease severity. Recently, myeloid-derived suppressor cells (MDSCs) have emerged as an immune cell population with an important role in MS. The monocytic-MDSCs (M-MDSCs) share the phenotype with Ly-6Chi-cells in the MS animal model, experimental autoimmune encephalomyelitis (EAE), and have been retrospectively related to the severity of the clinical course in the EAE. However, no data are available about the presence of M-MDSCs in the CNS of MS patients or its relation with the future disease aggressiveness. In this work, we show for the first time cells exhibiting all the bona-fide phenotypical markers of M-MDSCs associated with MS lesions, whose abundance in these areas appears to be directly correlated with longer disease duration in primary progressive MS patients. Moreover, we show that blood immunosuppressive Ly-6Chi-cells are strongly related to the future severity of EAE disease course. We found that a higher abundance of Ly-6Chi-cells at the onset of the EAE clinical course is associated with a milder disease course and less tissue damage. In parallel, we determined that the abundance of M-MDSCs in blood samples from untreated MS patients at their first relapse is inversely correlated with the Expanded Disability Status Scale (EDSS) at baseline and after a 1-year follow-up. In summary, our data point to M-MDSC load as a factor to be considered for future studies focused on the prediction of disease severity in EAE and MS.
Asunto(s)
Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Células Supresoras de Origen Mieloide , Animales , Ratones , Esclerosis Múltiple/patología , Células Supresoras de Origen Mieloide/patología , Estudios Retrospectivos , Encefalomielitis Autoinmune Experimental/patología , Progresión de la Enfermedad , Ratones Endogámicos C57BLRESUMEN
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide, seriously endangering human health. Although SARS-CoV-2 had a lower impact on paediatric population, children with COVID-19 have been reported as suffering from gastrointestinal (GI) symptoms at a higher rate than adults. The aim of this work was to evaluate faeces as a source of potential biomarkers of severity in the paediatric population, with an emphasis on intestinal microbiota and faecal immune mediators, trying to identify possible dysbiosis and immune intestinal dysfunction associated with the risk of hospitalization. This study involved 19 patients with COVID-19 under 24 months of age hospitalized during the pandemic at 6 different hospitals in Spain, and it included a comparable age-matched healthy control group (n = 18). Patients and controls were stratified according to their age in two groups: newborns or young infants (from 0 to 3 months old) and toddlers (infants from 6 to 24 months old). To characterize microbial intestinal communities, sequencing with Illumina technology of total 16S rDNA amplicons and internal transcribed spacer (ITS) amplicons of bifidobacteria were used. Faecal calprotectin (FC) and a range of human cytokines, chemokines, and growth factors were measured in faecal samples using ELISA and a multiplex system. Significant reduction in the abundance of sequences belonging to the phylum Actinobacteria was found in those infants with COVID-19, as well as in the Bifidobacteriaceae family. A different pattern of bifidobacteria was observed in patients, mainly represented by lower percentages of Bifidobacterium breve, as compared with controls. In the group of hospitalized young infants, FC was almost absent compared to age-matched healthy controls. A lower prevalence in faecal excretion of immune factors in these infected patients was also observed. CONCLUSION: Hospitalized infants with COVID-19 were depleted in some gut bacteria, such as bifidobacteria, in particular Bifidobacterium breve, which is crucial for the proper establishment of a functional intestinal microbiota, and important for the development of a competent immune system. Our results point to a possible immature immune system at intestine level in young infants infected by SARS-CoV2 requiring hospitalization. WHAT IS KNOWN: ⢠Although SARS-CoV-2 had a lower impact on paediatric population, children with COVID-19 have been reported as suffering from gastrointestinal symptoms at a higher rate than adults. ⢠Changes in microbial composition have been described in COVID-19 adult patients, although studies in children are limited. WHAT IS NEW: ⢠The first evidence that hospitalized infants with COVID-19 during the pandemic had a depletion in bifidobacteria, particularly in Bifidobacterium breve, beneficial gut bacteria in infancy that are crucial for the proper establishment of a competent immune system. ⢠In young infants (under 3 months of age) hospitalized with SARS-CoV2 infection, the aberrant bifidobacterial profile appears to overlap with a poor intestinal immune development as seen by calprotectin and the trend of immunological factors excreted in faeces.
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Bifidobacterium , COVID-19 , Adulto , Lactante , Recién Nacido , Humanos , Preescolar , Bifidobacterium/genética , Disbiosis , ARN Viral , SARS-CoV-2 , Heces/microbiología , Complejo de Antígeno L1 de LeucocitoRESUMEN
Plants and phytophagous arthropods have coevolved in a long battle for survival. Plants respond to phytophagous feeders by producing a battery of antiherbivore chemical defences, while herbivores try to adapt to their hosts by attenuating the toxic effect of the defence compounds. Cyanogenic glucosides are a widespread group of defence chemicals that come from cyanogenic plants. Among the non-cyanogenic ones, the Brassicaceae family has evolved an alternative cyanogenic pathway to produce cyanohydrin as a way to expand defences. When a plant tissue is disrupted by an herbivore attack, cyanogenic substrates are brought into contact with degrading enzymes that cause the release of toxic hydrogen cyanide and derived carbonyl compounds. In this review, we focus our attention on the plant metabolic pathways linked to cyanogenesis to generate cyanide. It also highlights the role of cyanogenesis as a key defence mechanism of plants to fight against herbivore arthropods, and we discuss the potential of cyanogenesis-derived molecules as alternative strategies for pest control.
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Artrópodos , Herbivoria , Animales , Plantas/metabolismo , Cianuros/metabolismo , Glicósidos/químicaRESUMEN
BACKGROUND AND PURPOSE: We aimed to determine whether an extended oral antibiotic prophylaxis protocol may reduce the rate of surgical site infection (SSI) in patients undergoing instrumented spinal fusion. PATIENTS AND METHODS: This retrospective cohort study comprise 901 consecutive patients subjected to spinal fusion between September 2011 and December 2018 with a minimum 1-year follow-up. 368 patients operated on between September 2011 and August 2014 were administered standard intravenous prophylaxis. 533 patients operated on between September 2014 and December 2018 were administered an extended protocol with 500 mg of oral cefuroxime axetil every 12 hours (clindamycin or levofloxacin in allergic individuals) until the removal of sutures. SSI was defined following the Centers for Disease Control and Prevention criteria. The association between risk factors and the incidence of SSI was evaluated by odds ratio (OR) with a multiple logistic regression model. RESULTS: The bivariate analysis showed a statistically significant association between SSI and the type of prophylaxis used ("extended"' = 1.7% vs. "standard" = 6.2%, p= 0.001), with a lower proportion of superficial SSIs with the extended regimen (0.8% vs. 4.1%, p = 0.001). The multiple logistic regression model showed an OR = 0.25 (95% confidence interval [CI] 0.10-0.53) for extended prophylaxis and an OR = 3.5 (CI 1.3-8.1) for non-beta-lactams antibiotics. CONCLUSION: Extended antibiotic prophylaxis seems to be associated with a reduction in the incidence of superficial SSI in instrumented spine surgery.
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Fusión Vertebral , Infección de la Herida Quirúrgica , Humanos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/etiología , Profilaxis Antibiótica/métodos , Estudios de Cohortes , Estudios Retrospectivos , Fusión Vertebral/efectos adversos , Estudios de Seguimiento , Antibacterianos/uso terapéuticoRESUMEN
BACKGROUND: The increasing number of treatments that are now available to manage patients with multiple sclerosis (MS) highlights the need to develop biomarkers that can be used within the framework of individualized medicine. Fingolimod is a disease-modifying treatment that belongs to the sphingosine-1-phosphate receptor modulators. In addition to inhibiting T cell egress from lymph nodes, fingolimod promotes the immunosuppressive activity of myeloid-derived suppressor cells (MDSCs), whose monocytic subset (M-MDSCs) can be used as a biomarker of disease severity, as well as the degree of demyelination and extent of axonal damage in the experimental autoimmune encephalomyelitis (EAE) model of MS. In the present study, we have assessed whether the abundance of circulating M-MDSCs may represent a useful biomarker of fingolimod efficacy in EAE and in the clinical context of MS patients. METHODS: Treatment with vehicle or fingolimod was orally administered to EAE mice for 14 days in an individualized manner, starting the day when each mouse began to develop clinical signs. Peripheral blood from EAE mice was collected previous to treatment and human peripheral blood mononuclear cells (PBMCs) were collected from fingolimod to treat MS patients' peripheral blood. In both cases, M-MDSCs abundance was analyzed by flow cytometry and its relationship with the future clinical affectation of each individual animal or patient was assessed. RESULTS: Fingolimod-treated animals presented a milder EAE course with less demyelination and axonal damage, although a few animals did not respond well to treatment and they invariably had fewer M-MDSCs prior to initiating the treatment. Remarkably, M-MDSC abundance was also found to be an important and specific parameter to distinguish EAE mice prone to better fingolimod efficacy. Finally, in a translational effort, M-MDSCs were quantified in MS patients at baseline and correlated with different clinical parameters after 12 months of fingolimod treatment. M-MDSCs at baseline were highly representative of a good therapeutic response to fingolimod, i.e., patients who met at least two of the criteria used to define non-evidence of disease activity-3 (NEDA-3) 12 months after treatment. CONCLUSION: Our data indicate that M-MDSCs might be a useful predictive biomarker of the response of MS patients to fingolimod.
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Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Células Supresoras de Origen Mieloide , Humanos , Animales , Ratones , Clorhidrato de Fingolimod/uso terapéutico , Células Supresoras de Origen Mieloide/patología , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/patología , Leucocitos Mononucleares , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/patología , BiomarcadoresRESUMEN
HOPs (HSP70-HSP90 organizing proteins) are a highly conserved family of HSP70 and HSP90 co-chaperones whose role in assisting the folding of various hormonal receptors has been extensively studied in mammals. In plants, HOPs are mainly associated with stress response, but their potential involvement in hormonal networks remains completely unexplored. In this article we describe that a member of the HOP family, HOP3, is involved in the jasmonic acid (JA) pathway and is linked to plant defense responses not only to pathogens, but also to a generalist herbivore. The JA pathway regulates responses to Botrytis cinerea infection and to Tetranychus urticae feeding; our data demonstrate that the Arabidopsis (Arabidopsis thaliana) hop3-1 mutant shows an increased susceptibility to both. The hop3-1 mutant exhibits reduced sensitivity to JA derivatives in root growth assays and downregulation of different JA-responsive genes in response to methyl jasmonate, further revealing the relevance of HOP3 in the JA pathway. Interestingly, yeast two-hybrid assays and in planta co-immunoprecipitation assays found that HOP3 interacts with COI1, suggesting that COI1 is a target of HOP3. Consistent with this observation, COI1 activity is reduced in the hop3-1 mutant. All these data strongly suggest that, specifically among HOPs, HOP3 plays a relevant role in the JA pathway by regulating COI1 activity in response to JA and, consequently, participating in defense signaling to biotic stresses.
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Proteínas de Arabidopsis/genética , Arabidopsis/fisiología , Ciclopentanos/farmacología , Chaperonas Moleculares/genética , Oxilipinas/farmacología , Reguladores del Crecimiento de las Plantas/farmacología , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Chaperonas Moleculares/metabolismo , Transducción de SeñalRESUMEN
Witches' broom disease of cacao is caused by the pathogenic fungus Moniliophthora perniciosa. By using tomato (Solanum lycopersicum) cultivar Micro-Tom (MT) as a model system, we investigated the physiological and metabolic consequences of M. perniciosa infection to determine whether symptoms result from sink establishment during infection. Infection of MT by M. perniciosa caused reductions in root biomass and fruit yield, a decrease in leaf gas exchange, and down-regulation of photosynthesis-related genes. The total leaf area and water potential decreased, while ABA levels, water conductance/conductivity, and ABA-related gene expression increased. Genes related to sugar metabolism and those involved in secondary cell wall deposition were up-regulated upon infection, and the concentrations of sugars, fumarate, and amino acids increased. 14C-glucose was mobilized towards infected MT stems, but not in inoculated stems of the MT line overexpressing CYTOKININ OXIDASE-2 (35S::AtCKX2), suggesting a role for cytokinin in establishing a sugar sink. The up-regulation of genes involved in cell wall deposition and phenylpropanoid metabolism in infected MT, but not in 35S::AtCKX2 plants, suggests establishment of a cytokinin-mediated sink that promotes tissue overgrowth with an increase in lignin. Possibly, M. perniciosa could benefit from the accumulation of secondary cell walls during its saprotrophic phase of infection.
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Agaricales , Cacao , Solanum lycopersicum , Agaricales/genética , Cacao/genética , Pared Celular , Citocininas , Solanum lycopersicum/genética , Solanum lycopersicum/microbiología , Enfermedades de las Plantas/microbiología , Azúcares , AguaRESUMEN
For decades, retinoids have been considered the gold standard of treatment for a variety of skin conditions.1,2 As the bioavailable form of vitamin A, retinoic acid has demonstrated the ability to reduce skin discoloration, stimulate collagen production, reduce rhytids, improve acne, and uneven skin texture.3,4 Retinoic acid is a potent drug with high bioavailability. Challenges with such a product include skin sensitivity and retinoid dermatitis.1,5 This potential irritation and discomfort may hinder patient compliance reducing visible results. The non-prescription vitamin A ingredient retinol is an effective and less irritating alternative, as it is converted into retinoic acid within the skin, causing little to no irritation when used topically. Intensive Age Refining Treatment: 0.5% pure retinol night by PCA SKIN® contains 0.5% retinol, protected and delivered into the skin with a multi-layered liposomal delivery technology. This development addresses the inherent instability of retinol,1,2,3 as well as the mitigation of irritation with the goal of enhancing patient compliance and visible results. This formulation also features niacinamide and terminalia chebula to further support the anti-aging benefits of retinol. The 12-week in vivo use of this potent, yet non-irritating retinol topical demonstrates improved patient compliance and satisfaction due to tolerability and enhanced efficacy in the improvement in overall signs of healthy skin. J Drugs Dermatol. 2022;21(7):784-788. doi:10.36849/JDD.6621.
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Envejecimiento de la Piel , Terminalia , Envejecimiento , Humanos , Niacinamida/efectos adversos , Retinoides , Tretinoina/efectos adversos , Vitamina A/efectos adversosRESUMEN
BACKGROUND: Rehabilitation services are an integral part of patient care, but in many developing countries, they are not prioritized and either unavailable or easily accessible to those who need them. Although the need for rehabilitation services is increasing in Honduras, rehabilitation workers are not included in the health care model that guides the care provided to communities, particularly in rural and remote areas. To understand the need for providing impactful rehabilitation services in disadvantaged communities, we explored the education and perception of the community relating to rehabilitation, investigated training available for rehabilitation workers, and examined the rehabilitation processes and practices in Northern Honduras from stakeholders' experiences. METHODS: We utilized a qualitative descriptive and interpretive approach grounded in case study methodology to understand rehabilitation education, process, and practice in Northern Honduras. Three rehabilitation centres were purposefully selected as the cases, and participants consisted of rehabilitation workers and managers from these centres. We collected data via interviews and focus group sessions. We analyzed the data via thematic analysis using NVivo version 12. RESULTS: In Northern Honduras, rehabilitation workers' limited training and continuing education, along with awareness about rehabilitation by community members and other health providers influence rehabilitation care. Although policies and initiatives to support people with disabilities and the broader community in need of rehabilitation exist, most policies are not applied in practice. The sustainability of rehabilitation services, which is rooted in charity, is challenged by the small range of funding opportunities strongly affecting rehabilitation care processes and clinical practices. The lack of trust and awareness from the medical profession towards rehabilitation workers sets a major barrier to referrals, interdisciplinary work, and quality of life for individuals in need of rehabilitation. CONCLUSION: This study advances knowledge of the need to increase understanding of rehabilitation care among community members and health providers, improve care processes and resources, and foster interprofessional practice, to enhance the quality of care and promote equitable care delivery, especially in rural and remote communities.
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Personas con Discapacidad , Calidad de Vida , Humanos , Honduras , Atención a la Salud , Educación ContinuaRESUMEN
Ovule primordia formation is a complex developmental process with a strong impact on the production of seeds. In Arabidopsis this process is controlled by a gene network, including components of the signalling pathways of auxin, brassinosteroids (BRs) and cytokinins. Recently, we have shown that gibberellins (GAs) also play an important role in ovule primordia initiation, inhibiting ovule formation in both Arabidopsis and tomato. Here we reveal that BRs also participate in the control of ovule initiation in tomato, by promoting an increase on ovule primordia formation. Moreover, molecular and genetic analyses of the co-regulation by GAs and BRs of the control of ovule initiation indicate that two different mechanisms occur in tomato and Arabidopsis. In tomato, GAs act downstream of BRs. BRs regulate ovule number through the downregulation of GA biosynthesis, which provokes stabilization of DELLA proteins that will finally promote ovule primordia initiation. In contrast, in Arabidopsis both GAs and BRs regulate ovule number independently of the activity levels of the other hormone. Taken together, our data strongly suggest that different molecular mechanisms could operate in different plant species to regulate identical developmental processes even, as for ovule primordia initiation, if the same set of hormones trigger similar responses, adding a new level of complexity.
Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Brasinoesteroides/metabolismo , Giberelinas/metabolismo , Solanum lycopersicum/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Solanum lycopersicum/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Transducción de Señal/genética , Transducción de Señal/fisiologíaRESUMEN
Ovule formation is a complex developmental process in plants, with a strong impact on the production of seeds. Ovule primordia initiation is controlled by a gene network, including components of the signaling pathways of auxin, brassinosteroids and cytokinins. By contrast, gibberellins (GAs) and DELLA proteins, the negative regulators of GA signaling, have never been shown to be involved in ovule initiation. Here, we provide molecular and genetic evidence that points to DELLA proteins as novel players in the determination of ovule number in Arabidopsis and in species of agronomic interest, such as tomato and rapeseed, adding a new layer of complexity to this important developmental process. DELLA activity correlates positively with ovule number, acting as a positive factor for ovule initiation. In addition, ectopic expression of a dominant DELLA in the placenta is sufficient to increase ovule number. The role of DELLA proteins in ovule number does not appear to be related to auxin transport or signaling in the ovule primordia. Possible crosstalk between DELLA proteins and the molecular and hormonal network controlling ovule initiation is also discussed.
Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/embriología , Giberelinas/metabolismo , Óvulo Vegetal/embriología , Arabidopsis/citología , Óvulo Vegetal/citologíaRESUMEN
MAIN CONCLUSION: A synthetic peptide from the C-terminal end of C4-phosphoenolpyruvate carboxylase is implicated in the proteolysis of the enzyme, and Glc-6P or phosphorylation of the enzyme modulate this effect. Phosphoenolpyruvate carboxylase (PEPC) is a cytosolic, homotetrameric enzyme that performs a variety of functions in plants. Among them, it is primarily responsible for CO2 fixation in the C4 photosynthesis pathway (C4-PEPC). Here we show that proteolysis of C4-PEPC by cathepsin proteases present in a semi-purified PEPC fraction was enhanced by the presence of a synthetic peptide containing the last 19 amino acids from the C-terminal end of the PEPC subunit (pC19). Threonine (Thr)944 and Thr948 in the peptide are important requirements for the pC19 effect. C4-PEPC proteolysis in the presence of pC19 was prevented by the PEPC allosteric effector glucose 6-phosphate (Glc-6P) and by phosphorylation of the enzyme. The role of these elements in the regulation of PEPC proteolysis is discussed in relation to the physiological context.
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Fosfoenolpiruvato Carboxilasa , Sorghum , Glucosa-6-Fosfato , Péptidos , Fosfoenolpiruvato Carboxilasa/metabolismo , Fosforilación , Fotosíntesis , Proteolisis , Sorghum/metabolismoRESUMEN
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.