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1.
EMBO J ; 42(13): e113004, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37211994

RESUMO

Soil salinity impairs plant growth reducing crop productivity. Toxic accumulation of sodium ions is counteracted by the Salt Overly Sensitive (SOS) pathway for Na+ extrusion, comprising the Na+ transporter SOS1, the kinase SOS2, and SOS3 as one of several Calcineurin-B-like (CBL) Ca2 + sensors. Here, we report that the receptor-like kinase GSO1/SGN3 activates SOS2, independently of SOS3 binding, by physical interaction and phosphorylation at Thr16. Loss of GSO1 function renders plants salt sensitive and GSO1 is both sufficient and required for activating the SOS2-SOS1 module in yeast and in planta. Salt stress causes the accumulation of GSO1 in two specific and spatially defined areas of the root tip: in the endodermis section undergoing Casparian strip (CS) formation, where it reinforces the CIF-GSO1-SGN1 axis for CS barrier formation; and in the meristem, where it creates the GSO1-SOS2-SOS1 axis for Na+ detoxification. Thus, GSO1 simultaneously prevents Na+ both from diffusing into the vasculature, and from poisoning unprotected stem cells in the meristem. By protecting the meristem, receptor-like kinase-conferred activation of the SOS2-SOS1 module allows root growth to be maintained in adverse environments.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Sódio/metabolismo , Nicho de Células-Tronco , Estresse Salino , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/metabolismo
2.
Proc Natl Acad Sci U S A ; 121(9): e2320657121, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38386704

RESUMO

To control net sodium (Na+) uptake, Arabidopsis plants utilize the plasma membrane (PM) Na+/H+ antiporter SOS1 to achieve Na+ efflux at the root and Na+ loading into the xylem, and the channel-like HKT1;1 protein that mediates the reverse flux of Na+ unloading off the xylem. Together, these opposing transport systems govern the partition of Na+ within the plant yet they must be finely co-regulated to prevent a futile cycle of xylem loading and unloading. Here, we show that the Arabidopsis SOS3 protein acts as the molecular switch governing these Na+ fluxes by favoring the recruitment of SOS1 to the PM and its subsequent activation by the SOS2/SOS3 kinase complex under salt stress, while commanding HKT1;1 protein degradation upon acute sodic stress. SOS3 achieves this role by direct and SOS2-independent binding to previously unrecognized functional domains of SOS1 and HKT1;1. These results indicate that roots first retain moderate amounts of salts to facilitate osmoregulation, yet when sodicity exceeds a set point, SOS3-dependent HKT1;1 degradation switches the balance toward Na+ export out of the root. Thus, SOS3 functionally links and co-regulates the two major Na+ transport systems operating in vascular plants controlling plant tolerance to salinity.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Transporte Proteico , Transporte Biológico , Proteólise , Osmorregulação , Trocadores de Sódio-Hidrogênio/genética , Proteínas de Arabidopsis/genética
3.
Plant Cell ; 35(1): 298-317, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36135824

RESUMO

The precise timing of flowering in adverse environments is critical for plants to secure reproductive success. We report a mechanism in Arabidopsis (Arabidopsis thaliana) controlling the time of flowering by which the S-acylation-dependent nuclear import of the protein SALT OVERLY SENSITIVE3/CALCINEURIN B-LIKE4 (SOS3/CBL4), a Ca2+-signaling intermediary in the plant response to salinity, results in the selective stabilization of the flowering time regulator GIGANTEA inside the nucleus under salt stress, while degradation of GIGANTEA in the cytosol releases the protein kinase SOS2 to achieve salt tolerance. S-acylation of SOS3 was critical for its nuclear localization and the promotion of flowering, but partly dispensable for salt tolerance. SOS3 interacted with the photoperiodic flowering components GIGANTEA and FLAVIN-BINDING, KELCH REPEAT, F-BOX1 and participated in the transcriptional complex that regulates CONSTANS to sustain the transcription of CO and FLOWERING LOCUS T under salinity. Thus, the SOS3 protein acts as a Ca2+- and S-acylation-dependent versatile regulator that fine-tunes flowering time in a saline environment through the shared spatial separation and selective stabilization of GIGANTEA, thereby connecting two signaling networks to co-regulate the stress response and the time of flowering.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Calcineurina/metabolismo , Cálcio/metabolismo , Estresse Salino , Regulação da Expressão Gênica de Plantas , Flores/metabolismo
4.
Proc Natl Acad Sci U S A ; 120(15): e2219693120, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37023134

RESUMO

Corticostriatal activity is an appealing target for nonpharmacological treatments of brain disorders. In humans, corticostriatal activity may be modulated with noninvasive brain stimulation (NIBS). However, a NIBS protocol with a sound neuroimaging measure demonstrating a change in corticostriatal activity is currently lacking. Here, we combine transcranial static magnetic field stimulation (tSMS) with resting-state functional MRI (fMRI). We first present and validate the ISAAC analysis, a well-principled framework that disambiguates functional connectivity between regions from local activity within regions. All measures of the framework suggested that the region along the medial cortex displaying greater functional connectivity with the striatum is the supplementary motor area (SMA), where we applied tSMS. We then use a data-driven version of the framework to show that tSMS of the SMA modulates the local activity in the SMA proper, in the adjacent sensorimotor cortex, and in the motor striatum. We finally use a model-driven version of the framework to clarify that the tSMS-induced modulation of striatal activity can be primarily explained by a change in the shared activity between the modulated motor cortical areas and the motor striatum. These results suggest that corticostriatal activity can be targeted, monitored, and modulated noninvasively in humans.


Assuntos
Córtex Motor , Córtex Sensório-Motor , Humanos , Corpo Estriado/diagnóstico por imagem , Neostriado , Córtex Motor/diagnóstico por imagem , Córtex Motor/fisiologia , Estimulação Magnética Transcraniana/métodos , Imageamento por Ressonância Magnética
5.
Proc Natl Acad Sci U S A ; 120(40): e2304032120, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37748063

RESUMO

Fairy circles (FCs) are regular vegetation patterns found in drylands of Namibia and Western Australia. It is virtually unknown whether they are also present in other regions of the world and which environmental factors determine their distribution. We conducted a global systematic survey and found FC-like vegetation patterns in 263 sites from 15 countries and three continents, including the Sahel, Madagascar, and Middle-West Asia. FC-like vegetation patterns are found in environments characterized by a unique combination of soil (including low nutrient levels and high sand content) and climatic (arid regions with high temperatures and high precipitation seasonality) conditions. In addition to these factors, the presence of specific biological elements (termite nests) in certain regions also plays a role in the presence of these patterns. Furthermore, areas with FC-like vegetation patterns also showed more stable temporal productivity patterns than those of surrounding areas. Our study presents a global atlas of FCs and provides unique insights into the ecology and biogeography of these fascinating vegetation patterns.


Assuntos
Clima Desértico , Ecologia , Geografia , Plantas , Animais
6.
Proc Natl Acad Sci U S A ; 119(33): e2207275119, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35939685

RESUMO

The circadian clock is a timekeeping, homeostatic system that temporally coordinates all major cellular processes. The function of the circadian clock is compensated in the face of variable environmental conditions ranging from normal to stress-inducing conditions. Salinity is a critical environmental factor affecting plant growth, and plants have evolved the SALT OVERLY SENSITIVE (SOS) pathway to acquire halotolerance. However, the regulatory systems for clock compensation under salinity are unclear. Here, we show that the plasma membrane Na+/H+ antiporter SOS1 specifically functions as a salt-specific circadian clock regulator via GIGANTEA (GI) in Arabidopsis thaliana. SOS1 directly interacts with GI in a salt-dependent manner and stabilizes this protein to sustain a proper clock period under salinity conditions. SOS1 function in circadian clock regulation requires the salt-mediated secondary messengers cytosolic free calcium and reactive oxygen species, pointing to a distinct regulatory role for SOS1 in addition to its function as a transporter to maintain Na+ homeostasis. Our results demonstrate that SOS1 maintains homeostasis of the salt response under high or daily fluctuating salt levels. These findings highlight the genetic capacity of the circadian clock to maintain timekeeping activity over a broad range of salinity levels.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ritmo Circadiano , Estresse Salino , Trocadores de Sódio-Hidrogênio , Arabidopsis/genética , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Estabilidade Proteica , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/metabolismo
7.
Pflugers Arch ; 476(1): 49-57, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37816992

RESUMO

The intensification of the stress response during resistance training (RT) under hypoxia conditions could trigger unwanted effects that compromise muscle health and, therefore, the ability of the muscle to adapt to longer training periods. We examined the effect of acute moderate terrestrial hypoxia on metabolic, inflammation, antioxidant capacity and muscle atrophy biomarkers after a single RT session in a young male population. Twenty healthy volunteers allocated to the normoxia (N < 700 m asl) or moderate altitude (HH = 2320 m asl) group participated in this study. Before and throughout the 30 min following the RT session (3 × 10 reps, 90 s rest, 70% 1RM), venous blood samples were taken and analysed for circulating calcium, inorganic phosphate, cytokines (IL-6, IL-10 and TNF-α), total antioxidant capacity (TAC) and myostatin. Main results displayed a marked metabolic stress response after the RT in both conditions. A large to very large proportional increase in the adjusted to pre-exercise change of inflammatory and anti-inflammatory markers favoured HH (serum TNF-α [ES = 1.10; p = 0.024] and IL-10 [ES = 1.31; p = 0.009]). The exercise produced a similar moderate increment of myostatin in both groups, followed by a moderate non-significant reduction in HH throughout the recovery (ES = - 0.72; p = 0.21). The RT slightly increased the antioxidant response regardless of the environmental condition. These results revealed no clear impact of RT under acute hypoxia on the metabolic, TAC and muscle atrophy biomarkers. However, a coordinated pro/anti-inflammatory response balances the potentiated effect of RT on systemic inflammation.


Assuntos
Altitude , Treinamento Resistido , Humanos , Masculino , Interleucina-10 , Antioxidantes , Miostatina , Fator de Necrose Tumoral alfa , Hipóxia , Inflamação , Biomarcadores , Músculos , Anti-Inflamatórios , Atrofia Muscular
8.
J Exp Bot ; 75(8): 2481-2493, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38280208

RESUMO

The plant hormone abscisic acid (ABA) is an important regulator of plant growth and development and plays a crucial role in both biotic and abiotic stress responses. ABA modulates flowering time, but the precise molecular mechanism remains poorly understood. Here we report that ABA INSENSITIVE 2 (ABI2) is the only phosphatase from the ABA-signaling core that positively regulates the transition to flowering in Arabidopsis. Loss-of-function abi2-2 mutant shows significantly delayed flowering both under long day and short day conditions. Expression of floral repressor genes such as FLOWERING LOCUS C (FLC) and CYCLING DOF FACTOR 1 (CDF1) was significantly up-regulated in abi2-2 plants while expression of the flowering promoting genes FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) was down-regulated. Through genetic interactions we further found that ost1-3 and abi5-1 mutations are epistatic to abi2-2, as both of them individually rescued the late flowering phenotype of abi2-2. Interestingly, phosphorylation and protein stability of ABA INSENSITIVE 5 (ABI5) were enhanced in abi2-2 plants suggesting that ABI2 dephosphorylates ABI5, thereby reducing protein stability and the capacity to induce FLC expression. Our findings uncovered the unexpected role of ABI2 in promoting flowering by inhibiting ABI5-mediated FLC expression in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Regulação da Expressão Gênica de Plantas , Fosforilação , Reguladores de Crescimento de Plantas/metabolismo , Proteínas Quinases/metabolismo
9.
J Neurol Neurosurg Psychiatry ; 95(3): 206-213, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-37673642

RESUMO

BACKGROUND: Unilateral focused ultrasound subthalamotomy (FUS-STN) improves motor features of Parkinson's disease (PD) in moderately advanced patients. The less invasive nature of FUS makes its early application in PD feasible. We aim to assess the safety and efficacy of unilateral FUS-STN in patients with PD of less than 5 years from diagnosis (early PD). METHODS: Prospective, open-label study. Eligible patients with early PD had highly asymmetrical cardinal features. The primary outcome was safety, defined as treatment-related adverse events at 6 months. Secondary outcomes included efficacy, assessed as motor improvement in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), motor fluctuations, non-motor symptoms, daily living activities, quality of life, medication and patients' impression of change. RESULTS: Twelve patients with PD (median age 52.0 (IQR 49.8-55.3) years, median time from diagnosis 3.0 (2.1-3.9) years) underwent unilateral FUS-STN. Within 2 weeks after treatment, five patients developed dyskinesia on the treated side, all resolved after levodopa dose adjustment. One patient developed mild contralateral motor weakness which fully resolved in 4 weeks. One patient developed dystonic foot and another hand and foot dystonia. The latter impaired gait and became functionally disabling initially. Both cases were well controlled with botulinum toxin injections. The off-medication motor MDS-UPDRS score for the treated side improved at 12 months by 68.7% (from 14.5 to 4.0, p=0.002), and the total motor MDS-UPDRS improved by 49.0% (from 26.5 to 13.0, p=0.002). Eleven patients (92%) reported global improvement 12 months after treatment. CONCLUSION: Unilateral FUS-STN may be safe and effective to treat motor manifestations in patients with early PD. A larger confirmatory trial is warranted. TRIAL REGISTRATION NUMBER: NCT04692116.


Assuntos
Doença de Parkinson , Humanos , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Projetos Piloto , Qualidade de Vida , Estudos Prospectivos , Resultado do Tratamento , Levodopa
10.
Artigo em Inglês | MEDLINE | ID: mdl-38760152

RESUMO

BACKGROUND: The nigrostriatal system is especially vulnerable to neurodegeneration in Parkinson's disease (PD) and the blood-brain barrier (BBB) is a limiting factor for delivery of therapeutic agents to the brain. This pilot study aimed to demonstrate safety, feasibility and tissue penetration (by 18F-Choline-positron emission tomography (PET)) of MR-guided focused ultrasound (MRgFUS) simultaneous BBB opening (BBB-O) in the substantia nigra (SN) and putamen in PD. METHODS: Three patients underwent MRgFUS for midbrain and putamen BBB-O. Patients were evaluated clinically and underwent brain MRI with gadolinium (baseline, 24 hours, 14 days and 3 months postprocedure). In two patients, BBB-O was repeated after 2-3 weeks, and 18F-Choline-PET was performed immediately after. RESULTS: The right SN and putamen were simultaneously opened unilaterally in 3 patients once and the left SN in 1 patient in a different session. No severe clinical or neuroimaging adverse events developed in any patient. 18F-Choline-PET uptake was enhanced in the targeted SN and putamen regions. CONCLUSION: BBB-O of the nigrostriatal system is a feasible and well-tolerated approach in patients with PD. 18F-Choline-PET uptake indicates penetration into the parenchyma after BBB-O, which suggests that the opening is functionally effective. This minimally invasive technique could facilitate delivery of putative neurorestorative molecules to brain regions vulnerable to neurodegeneration.

11.
Rev Esp Enferm Dig ; 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38205690

RESUMO

Endoscopic retrograde cholangiopancreatography (ERCP) performed in situations of altered anatomy has been described. Thus, in cases of Roux-en-Y gastric by-pass, several approaches have been documented for performing ERCP: by enteroscopy, guided by laparoscopic approach through the gastric remnant, and direct transgastric guided by endoscopic ultrasound through a stent between the reservoir or alimentary loop and the gastric remnant. However, there are clinical situations in which the anatomy is not altered, but there may be pancreatic lesions subsidiary to study by endoscopic ultrasound in situations where the endoscope cannot pass through the esophagus. Therefore, we present the clinical case of a patient with a pancreatic lesion subsidiary to study and a distal esophageal adenocarcinoma that prevented the passage of the endoscope.

12.
Rev Esp Enferm Dig ; 116(1): 46-47, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37073711

RESUMO

An analysis of the prognostic impact of up to 36 immuno-inflammatory indices at 3 different times during the diagnostic-therapeutic process for gastric cancer. The dependent variable was disease-free survival at 3 years. The independent factors obtained were combined with TNM to provide an improved prognostic model.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Prognóstico , Projetos Piloto , Estadiamento de Neoplasias , Intervalo Livre de Doença , Estudos Retrospectivos
13.
N Engl J Med ; 383(26): 2501-2513, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33369354

RESUMO

BACKGROUND: The subthalamic nucleus is the preferred neurosurgical target for deep-brain stimulation to treat cardinal motor features of Parkinson's disease. Focused ultrasound is an imaging-guided method for creating therapeutic lesions in deep-brain structures, including the subthalamic nucleus. METHODS: We randomly assigned, in a 2:1 ratio, patients with markedly asymmetric Parkinson's disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure. The primary efficacy outcome was the between-group difference in the change from baseline to 4 months in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (i.e., part III) for the more affected body side (range, 0 to 44, with higher scores indicating worse parkinsonism) in the off-medication state. The primary safety outcome (procedure-related complications) was assessed at 4 months. RESULTS: Among 40 enrolled patients, 27 were assigned to focused ultrasound subthalamotomy (active treatment) and 13 to the sham procedure (control). The mean MDS-UPDRS III score for the more affected side decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points; 95% confidence interval [CI], 8.6 to 11.1) and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points; 95% CI, 0.0 to 3.5); the between-group difference was 8.1 points (95% CI, 6.0 to 10.3; P<0.001). Adverse events in the active-treatment group were dyskinesia in the off-medication state in 6 patients and in the on-medication state in 6, which persisted in 3 and 1, respectively, at 4 months; weakness on the treated side in 5 patients, which persisted in 2 at 4 months; speech disturbance in 15 patients, which persisted in 3 at 4 months; facial weakness in 3 patients, which persisted in 1 at 4 months; and gait disturbance in 13 patients, which persisted in 2 at 4 months. In 6 patients in the active-treatment group, some of these deficits were present at 12 months. CONCLUSIONS: Focused ultrasound subthalamotomy in one hemisphere improved motor features of Parkinson's disease in selected patients with asymmetric signs. Adverse events included speech and gait disturbances, weakness on the treated side, and dyskinesia. (Funded by Insightec and others; ClinicalTrials.gov number, NCT03454425.).


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Doença de Parkinson/cirurgia , Núcleo Subtalâmico/cirurgia , Adulto , Idoso , Método Duplo-Cego , Discinesias/etiologia , Feminino , Transtornos Neurológicos da Marcha/etiologia , Ablação por Ultrassom Focalizado de Alta Intensidade/efeitos adversos , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Destreza Motora , Doença de Parkinson/fisiopatologia , Complicações Pós-Operatórias , Índice de Gravidade de Doença , Distúrbios da Fala/etiologia
14.
Brain ; 145(3): 1018-1028, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35349639

RESUMO

The striatal dopaminergic deficit in Parkinson's disease exhibits a typical pattern, extending from the caudal and dorsal putamen at onset to its more rostral region as the disease progresses. Clinically, upper-limb onset of cardinal motor features is the rule. Thus, according to current understanding of striatal somatotopy (i.e. the lower limb is dorsal to the upper limb) the assumed pattern of early dorsal striatal dopaminergic denervation in Parkinson's disease does not fit with an upper-limb onset. We have examined the topography of putaminal denervation in a cohort of 23 recently diagnosed de novo Parkinson's disease patients and 19 age-/gender-matched healthy subjects assessed clinically and by 18F-DOPA PET; 15 patients were re-assessed after 2 years. There was a net upper-limb predominance of motor features at onset. Caudal denervation of the putamen was confirmed in both the more- and less-affected hemispheres and corresponding hemibodies. Spatial covariance analysis of the most affected hemisphere revealed a pattern of 18F-DOPA uptake rate deficit that suggested focal dopamine loss starting in the posterolateral and intermediate putamen. Functional MRI group-activation maps during a self-paced motor task were used to represent the somatotopy of the putamen and were then used to characterize the decline in 18F-DOPA uptake rate in the upper- and lower-limb territories. This showed a predominant decrement in both hemispheres, which correlated significantly with severity of bradykinesia. A more detailed spatial analysis revealed a dorsoventral linear gradient of 18F-DOPA uptake rate in Parkinson's disease patients, with the highest putamen denervation in the caudal intermediate subregion (dorsoventral plane) compared to healthy subjects. The latter area coincides with the functional representation of the upper limb. Clinical motor assessment at 2-year follow-up showed modest worsening of parkinsonism in the primarily affected side and more noticeable increases in the upper limb in the less-affected side. Concomitantly, 18F-DOPA uptake rate in the less-affected putamen mimicked that recognized on the most-affected side. Our findings suggest that early dopaminergic denervation in Parkinson's disease follows a somatotopically related pattern, starting with the upper-limb representation in the putamen and progressing over a 2-year period in the less-affected hemisphere. These changes correlate well with the clinical presentation and evolution of motor features. Recognition of a precise somatotopic onset of nigrostriatal denervation may help to better understand the onset and progression of dopaminergic neurodegeneration in Parkinson's disease and eventually monitor the impact of putative therapies.


Assuntos
Doença de Parkinson , Pré-Escolar , Corpo Estriado/diagnóstico por imagem , Denervação , Di-Hidroxifenilalanina , Dopamina/fisiologia , Humanos , Doença de Parkinson/diagnóstico por imagem , Putamen/diagnóstico por imagem
15.
Proc Natl Acad Sci U S A ; 117(48): 30805-30815, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33199617

RESUMO

Transcriptional regulation is a complex and pivotal process in living cells. HOS15 is a transcriptional corepressor. Although transcriptional repressors generally have been associated with inactive genes, increasing evidence indicates that, through poorly understood mechanisms, transcriptional corepressors also associate with actively transcribed genes. Here, we show that HOS15 is the substrate receptor for an SCF/CUL1 E3 ubiquitin ligase complex (SCFHOS15) that negatively regulates plant immunity by destabilizing transcriptional activation complexes containing NPR1 and associated transcriptional activators. In unchallenged conditions, HOS15 continuously eliminates NPR1 to prevent inappropriate defense gene expression. Upon defense activation, HOS15 preferentially associates with phosphorylated NPR1 to stimulate rapid degradation of transcriptionally active NPR1 and thus limit the extent of defense gene expression. Our findings indicate that HOS15-mediated ubiquitination and elimination of NPR1 produce effects contrary to those of CUL3-containing ubiquitin ligase that coactivate defense gene expression. Thus, HOS15 plays a key role in the dynamic regulation of pre- and postactivation host defense.


Assuntos
Proteínas Correpressoras/metabolismo , Regulação da Expressão Gênica de Plantas , Imunidade Vegetal , Fenômenos Fisiológicos Vegetais , Proteínas de Plantas/metabolismo , Ativação Transcricional , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Complexos Multiproteicos , Ligação Proteica , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
16.
Psychiatry Clin Neurosci ; 77(4): 223-232, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36579893

RESUMO

AIM: Impulse-control disorder is a common neuropsychiatric complication in Parkinson's disease (PD) under dopamine replacement therapy. Prior studies tested the balance between enhanced desire towards reward and cognitive control deficits, hypothesized to be biased towards the former in impulse control disorders. We provide evidence for this hypothesis by measuring behavioral and neural patterns behind the influence of sexual desire over response inhibition and tools towards functional restoration using repetitive transcranial stimulation in patients with hypersexuality as predominant impulsive disorder. METHODS: The effect of sexual cues on inhibition was measured with a novel erotic stop-signal task under on and off dopaminergic medication. Task-related functional and anatomical connectivity models were estimated in 16 hypersexual and 17 nonhypersexual patients with PD as well as in 17 healthy controls. Additionally, excitatory neuromodulation using intermittent theta-burst stimulation (sham-controlled) was applied over the pre-supplementary motor area in 20 additional hypersexual patients with PD aiming to improve response inhibition. RESULTS: Compared with their nonhypersexual peers, patients with hypersexuality recruited caudate, pre-supplementary motor area, ventral tegmental area, and anterior cingulate cortex while on medication. Reduced connectivity was found between pre-supplementary motor area and caudate nucleus in hypersexual compared with nonhypersexual patients (while medicated), a result paralleled by compensatory enhanced anatomical connectivity. Furthermore, stimulation over the pre-supplementary motor area improved response inhibition in hypersexual patients with PD when exposed to sexual cues. CONCLUSION: This study, therefore, has identified a specific fronto-striatal and mesolimbic circuitry underlying uncontrolled sexual responses in medicated patients with PD where cortical neuromodulation halts its expression.


Assuntos
Doença de Parkinson , Humanos , Dopamina/metabolismo , Giro do Cíngulo/metabolismo , Comportamento Impulsivo , Imageamento por Ressonância Magnética , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Estudos de Casos e Controles
17.
Sensors (Basel) ; 23(6)2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36991991

RESUMO

In this work, we present power and quality measurements of four transmissions using different emission technologies in an indoor environment, specifically a corridor, at the frequency of 868 MHz under two non-line-of-sight (NLOS) conditions. A narrowband (NB) continuous wave (CW) signal has been transmitted, and its received power has been measured with a spectrum analyzer, LoRa and Zigbee signals have also been transmitted, and their Received Signal Strength Indicator (RSSI) and bit error rate (BER) have been measured using the transceivers themselves; finally, a 20 MHz bandwidth 5G QPSK signal has also been transmitted and their quality parameters, such as SS-RSRP, SS-RSRQ and SS-RINR, have been measured using a SA. Thereafter, two fitting models, the Close-in (CI) model and the Floating-Intercept (FI) model, were used to analyze the path loss. The results show that slopes below 2 for the NLOS-1 zone and above 3 for the NLOS-2 zone have been found. Moreover, the CI and FI model behave very similarly in the NLOS-1 zone, while in the NLOS-2 zone, the CI model has poor accuracy in contrast to the FI model, which achieves the best accuracy in both NLOS situations. From these models, the power predicted with the FI model has been correlated with the measured BER value, and power margins have been established for which LoRa and Zigbee would each reach a BER greater than 5%; likewise, -18 dB has been established for the SS-RSRQ of 5G transmission.

18.
Int J Mol Sci ; 24(4)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36834961

RESUMO

Plants have evolved elaborate mechanisms to sense, respond to and overcome the detrimental effects of high soil salinity. The role of calcium transients in salinity stress signaling is well established, but the physiological significance of concurrent salinity-induced changes in cytosolic pH remains largely undefined. Here, we analyzed the response of Arabidopsis roots expressing the genetically encoded ratiometric pH-sensor pHGFP fused to marker proteins for the recruitment of the sensor to the cytosolic side of the tonoplast (pHGFP-VTI11) and the plasma membrane (pHGFP-LTI6b). Salinity elicited a rapid alkalinization of cytosolic pH (pHcyt) in the meristematic and elongation zone of wild-type roots. The pH-shift near the plasma membrane preceded that at the tonoplast. In pH-maps transversal to the root axis, the epidermis and cortex had cells with a more alkaline pHcyt relative to cells in the stele in control conditions. Conversely, seedlings treated with 100 mM NaCl exhibited an increased pHcyt in cells of the vasculature relative to the external layers of the root, and this response occurred in both reporter lines. These pHcyt changes were substantially reduced in mutant roots lacking a functional SOS3/CBL4 protein, suggesting that the operation of the SOS pathway mediated the dynamics of pHcyt in response to salinity.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Raízes de Plantas , Salinidade , Transdução de Sinais , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Membrana Celular/metabolismo , Membrana Celular/fisiologia , Raízes de Plantas/metabolismo , Raízes de Plantas/fisiologia , Cloreto de Sódio/farmacologia , Transdução de Sinais/fisiologia
19.
Int J Mol Sci ; 24(5)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36902215

RESUMO

Poly(ADP-ribose) polymerase-1 (PARP-1) is a protein involved in multiple physiological processes. Elevated PARP-1 expression has been found in several tumours, being associated with stemness and tumorigenesis. In colorectal cancer (CRC), some controversy among studies has been described. In this study, we analysed the expression of PARP-1 and cancer stem cell (CSC) markers in CRC patients with different p53 status. In addition, we used an in vitro model to evaluate the influence of PARP-1 in CSC phenotype regarding p53. In CRC patients, PARP-1 expression correlated with the differentiation grade, but this association was only maintained for tumours harbouring wild-type p53. Additionally, in those tumours, PARP-1 and CSC markers were positively correlated. In mutated p53 tumours, no associations were found, but PARP-1 was an independent factor for survival. According to our in vitro model, PARP-1 regulates CSC phenotype depending on p53 status. PARP-1 overexpression in a wild type p53 context increases CSC markers and sphere forming ability. By contrast, those features were reduced in mutated p53 cells. These results could implicate that patients with elevated PARP-1 expression and wild type p53 could benefit from PARP-1 inhibition therapies, meanwhile it could have adverse effects for those carrying mutated p53 tumours.


Assuntos
Neoplasias Colorretais , Células-Tronco Neoplásicas , Poli(ADP-Ribose) Polimerase-1 , Proteína Supressora de Tumor p53 , Humanos , Neoplasias Colorretais/metabolismo , Células-Tronco Neoplásicas/metabolismo , Fenótipo , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Proteína Supressora de Tumor p53/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo
20.
Molecules ; 28(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36677786

RESUMO

The increasing demand for superfoods has resulted in an increase in chia seeds consumption. The reintroduction of this ancient crop in agriculture is useful to ensure food security since it can grow in high-stress conditions. The current study aimed to characterize chia seeds, cold-pressed oil, and defatted cake (the oil extraction by-product) to improve their value and to meet consumer's expectations (low-fat products). Chia seeds presented a significantly higher energy value than cake (444 vs. 284 kcal/100 g, respectively) due to fat removal (33 vs. 7%). The cake showed higher contents of total minerals (6 vs. 5%), protein (27 vs. 18%), and fiber (48 vs. 38%) in comparison to the seeds, and was hence considered a promising food ingredient. The major fatty acid in oil, seeds, and cake was α-linolenic acid (62-66%), and the vitamin E content was 409, 200, and 44 mg/kg, respectively. The major amino acid in the seeds and cake was glutamic acid (49 vs. 36 mg/g). The oil had a low oxidative stability (1 h), and the total phenolics content was 1.3 mg gallic acid equivalents/100 g. Chia cake incorporation in food formulations will follow consumer's interests, and the obtained oil can be used to improve the oil supply for different applications. This approach adds value to the concept of "one health" since it includes the culture, the environment, and the consumers.


Assuntos
Salvia , Sementes , Sementes/química , Extratos Vegetais/análise , Ácidos Graxos/análise , Grão Comestível/metabolismo , Óleos de Plantas/química , Salvia/química
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