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Matcha tea is obtained from Camellia sinensis plants grown in the shade and is consumed as a whole powder of the leaves. Matcha is reported to have a high content of bioactive components, such as catechins and quercetin, which underlie some of its biological properties. The study consists of the evaluation of the antiglycative effects and antioxidant potential of extracts derived from Grade 1 and Grade 4 matcha tea supported by the phytochemical analysis of the contained relevant antioxidant compounds. The aqueous extracts from matcha powders were prepared in an ultrasonic bath at 60 and 80 °C. All the extracts showed a significant antiglycative activity. For all the extracts levels of antioxidant compounds as well as antioxidant potential were significantly high. Results obtained suggest the potential of matcha tea as an ingredient for nutraceutical and pharmaceutical applications.

The seed habit is the most complex and successful method of sexual reproduction in vascular plants. It represents a remarkable moment in the evolution of plants that afterward spread on land. In particular, seed size had a pivotal role in evolutionary success and agronomic traits, especially in the field of crop domestication. Given that crop seeds constitute one of the primary products for consumption, it follows that seed size represents a fundamental determinant of crop yield. This adaptative feature is strictly controlled by genetic traits from both maternal and zygotic tissues, although seed development and growth are also affected by environmental cues. Despite being a highly exploited topic for both basic and applied research, there are still many issues to be elucidated for developmental biology as well as for agronomic science. This review addresses a number of open questions related to cues that influence seed growth and size and how they influence seed germination. Moreover, new insights on the genetic-molecular control of this adaptive trait are presented.

The increase in soil salinization represents a current challenge for plant productivity, as most plants, including crops, are mainly salt-sensitive species. The identification of molecular traits underpinning salt tolerance represents a primary goal for breeding programs. In this scenario, the study of intraspecific variability represents a valid tool for investigating natural genetic resources evolved by plants in different environmental conditions. As a model system, Arabidopsis thaliana, including over 750 natural accessions, represents a species extensively studied at phenotypic, metabolic, and genomic levels under different environmental conditions. Two haplogroups showing opposite root architecture (shallow or deep roots) in response to auxin flux perturbation were identified and associated with EXO70A3 locus variations. Here, we studied the influence of these genetic backgrounds on plant salt tolerance. Eight accessions belonging to the two haplogroups were tested for salt sensitivity by exposing them to moderate (75 mM NaCl) or severe (150 mM NaCl) salt stress. Salt-tolerant accessions were found in both haplogroups, and all of them showed efficient ROS-scavenging ability. Even if an exclusive relation between salt tolerance and haplogroup membership was not observed, the modulation of root system architecture might also contribute to salt tolerance.

The safeguarding of plant health is vital for optimizing crop growth practices, especially in the face of the biggest challenges of our generation, namely the environmental crisis and the dramatic changes in the climate. Among the many innovative tools developed to address these issues, wearable sensors have recently been proposed for monitoring plant growth and microclimates in a sustainable manner. These systems are composed of flexible matrices with embedded sensing elements, showing promise in revolutionizing plant monitoring without being intrusive. Despite their potential benefits, concerns arise regarding the effects of the long-term coexistence of these devices with the plant surface. Surprisingly, a systematic analysis of their influence on plant physiology is lacking. This study aims to investigate the effect of the color and geometric features of flexible matrices on two key plant physiological functions: photosynthesis and transpiration. Our findings indicate that the negative effects associated with colored substrates, as identified in recent research, can be minimized by holing the matrix surface with a percentage of voids of 15.7%. This approach mitigates interference with light absorption and reduces water loss to a negligible extent, making our work one of the first pioneering efforts in understanding the intricate relationship between plant wearables' features and plant health.

Plants synthesize ascorbate (ASC) via the D-mannose/L-galactose pathway whereas animals produce ASC and H 2 O 2 via the UDP-glucose pathway, with Gulono-1,4 γ-lactone oxidases (GULLO) as the last step. A. thaliana has seven isoforms, GULLO1-7; previous in silico analysis suggested that GULLO2, mostly expressed in developing seeds, might be involved in iron (Fe) nutrition. We isolated atgullo2-1 and atgullo2-2 mutants, quantified ASC and H 2 O 2 in developing siliques, Fe(III) reduction in immature embryos and seed coats. Surfaces of mature seed coats were analysed via atomic force and electron microscopies; suberin monomer and elemental compositions of mature seeds, including Fe, were profiled via chromatography and inductively coupled plasma-mass spectrometry. Lower levels of ASC and H 2 O 2 in atgullo2 immature siliques are accompanied by an impaired Fe(III) reduction in seed coats and lower Fe content in embryos and seeds; atgullo2 seeds displayed reduced permeability and higher levels of C18:2 and C18:3 ω-hydroxyacids, the two predominant suberin monomers in A. thaliana seeds. We propose that GULLO2 contributes to ASC synthesis, for Fe(III) reduction into Fe(II). This step is critical for Fe transport from endosperm into developing embryos. We also show that alterations in GULLO2 activity affect suberin biosynthesis and accumulation in the seed coat., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The devastating effects of global climate change on crop production and exponential population growth pose a major challenge to agricultural yields. To cope with this problem, crop performance monitoring is becoming increasingly necessary. In this scenario, the use of sensors and biosensors capable of detecting changes in plant fitness and predicting the evolution of their morphology and physiology has proven to be a useful strategy to increase crop yields. Flexible sensors and nanomaterials have inspired the emerging fields of wearable and on-plant portable devices that provide continuous and accurate long-term sensing of morphological, physiological, biochemical, and environmental parameters. This review provides an overview of novel plant sensing technologies by discussing wearable and integrated devices proposed for engineering plant and monitoring its morphological traits and physiological processes, as well as plant-environment interactions. For each application scenario, the state-of-the-art sensing solutions are grouped according to the plant organ on which they have been installed highlighting their main technological advantages and features. Finally, future opportunities, challenges and perspectives are discussed. We anticipate that the application of this technology in agriculture will provide more accurate measurements for farmers and plant scientists with the ability to track crop performance in real time. All of this information will be essential to enable rapid optimization of plants development through tailored treatments that improve overall plant health even under stressful conditions, with the ultimate goal of increasing crop productivity in a more sustainable manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Wearable devices are widely spreading in various scenarios for monitoring different parameters related to human and recently plant health. In the context of precision agriculture, wearables have proven to be a valuable alternative to traditional measurement methods for quantitatively monitoring plant development. This study proposed a multi-sensor wearable platform for monitoring the growth of plant organs (i.e., stem and fruit) and microclimate (i.e., environmental temperature-T and relative humidity-RH). The platform consists of a custom flexible strain sensor for monitoring growth when mounted on a plant and a commercial sensing unit for monitoring T and RH values of the plant surrounding. A different shape was conferred to the strain sensor according to the plant organs to be engineered. A dumbbell shape was chosen for the stem while a ring shape for the fruit. A metrological characterization was carried out to investigate the strain sensitivity of the proposed flexible sensors and then preliminary tests were performed in both indoor and outdoor scenarios to assess the platform performance. The promising results suggest that the proposed system can be considered one of the first attempts to design wearable and portable systems tailored to the specific plant organ with the potential to be used for future applications in the coming era of digital farms and precision agriculture.

Global climate change and exponential population growth pose a challenge to agricultural outputs. In this scenario, novel techniques have been proposed to improve plant growth and increase crop yields. Wearable sensors are emerging as promising tools for the non-invasive monitoring of plant physiological and microclimate parameters. Features of plant wearables, such as easy anchorage to different organs, compliance with natural surfaces, high flexibility, and biocompatibility, allow for the detection of growth without impacting the plant functions. This work proposed two wearable sensors based on fiber Bragg gratings (FBGs) within silicone matrices. The use of FBGs is motivated by their high sensitivity, multiplexing capacities, and chemical inertia. Firstly, we focused on the design and the fabrication of two plant wearables with different matrix shapes tailored to specific plant organs (i.e., tobacco stem and melon fruit). Then, we described the sensors' metrological properties to investigate the sensitivity to strain and the influence of environmental factors, such as temperature and humidity, on the sensors' performance. Finally, we performed experimental tests to preliminary assess the capability of the proposed sensors to monitor dimensional changes of plants in both laboratory and open field settings. The promising results will foster key actions to improve the use of this innovative technology in smart agriculture applications for increasing crop products quality, agricultural efficiency, and profits.

Heterozygous mutations in the gene coding for progranulin (GRN) cause frontotemporal lobar degeneration (FTLD) while homozygous mutations are linked to neuronal ceroidolipofuscinosis (NCL). While both FTLD/NCL pathological hallmarks were mostly investigated in heterozygous GRN+/- brain tissue or induced pluripotent stem cell (iPSC)-derived neurons, data from homozygous GRN-/- condition are scarce, being limited to a postmortem brain tissue from a single case. Indeed, homozygous GRN-/- is an extremely rare condition reported in very few cases. Our aim was to investigate pathological phenotypes associated with FTLD and NCL in iPSC-derived cortical neurons from a GRN-/- patient affected by NCL. iPSCs were generated from peripheral blood of a GRN wt healthy donor and a GRN-/- patient and subsequently differentiated into cortical neurons. Several pathological changes were investigated, by means of immunocytochemical, biochemical and ultrastructural analyses. GRN-/- patient-derived cortical neurons displayed both TDP-43 and phospho-TDP-43 mislocalization, enlarged autofluorescent lysosomes and electron-dense vesicles containing storage material with granular, curvilinear and fingerprints profiles. In addition, different patterns in the expression of TDP-43, caspase 3 and cleaved caspase 3 were observed by biochemical analysis at different time points of cortical differentiation. At variance with previous findings, the present data highlight the existence of both FTLD- and NCL-linked pathological features in GRN-/- iPSC-derived cortical neurons from a NCL patient. They also suggest an evolution in the appearance of these features: firstly, FTLD-related TDP-43 alterations and initial NCL storage materials were detected; afterwards, mainly well-shaped NCL storage materials were present, while some FTLD features were not observed anymore., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Frontotemporal lobar degeneration (FTLD) is a complex disease, characterized by progressive degeneration of frontal and temporal lobes. Mutations in progranulin ( GRN ) gene have been found in up to 50% of patients with familial FTLD. Abnormal deposits of post-translationally-modified TAR DNA-binding protein of 43 kDa (TDP-43) represent one of the main hallmarks of the brain pathology. To investigate in peripheral cells the presence of the different TDP-43 forms, especially the toxic 25 kDa fragments, we analyzed lymphoblastoid cell lines (LCLs) and the derived extracellular vesicles (EVs) from patients carrying a GRN mutation, together with wild-type (WT) healthy controls. After characterizing EV sizes and concentrations by nanoparticle tracking analysis, we investigated the levels of different forms of the TDP-43 protein in LCLs and respective EVs by Western blot. Our results showed a trend of concentration decreasing in EVs derived from GRN -mutated LCLs, although not reaching statistical significance. A general increase in p-TDP-43 levels in GRN -mutated LCLs and EVs was observed. In particular, the toxic 25 kDa fragments of p-TDP-43 were only present in GRN-mutated LCLs and were absent in the WT controls. Furthermore, these fragments appeared to be more concentrated in EVs than in LCLs, suggesting a relevant role of EVs in spreading pathological molecules between cells.

Emerging data suggest the roles of endo-lysosomal dysfunctions in frontotemporal lobar degeneration (FTLD) and in other dementias. Cathepsin D is one of the major lysosomal proteases, mediating the degradation of unfolded protein aggregates. In this retrospective study, we investigated cathepsin D levels in human plasma and in the plasma small extracellular vesicles (sEVs) of 161 subjects (40 sporadic FTLD, 33 intermediate/pathological C9orf72 expansion carriers, 45 heterozygous/homozygous GRN mutation carriers, and 43 controls). Cathepsin D was quantified by ELISA, and nanoparticle tracking analysis data (sEV concentration for the cathepsin D level normalization) were extracted from our previously published dataset or were newly generated. First, we revealed a positive correlation of the cathepsin D levels with the age of the patients and controls. Even if no significant differences were found in the cathepsin D plasma levels, we observed a progressive reduction in plasma cathepsin D moving from the intermediate to C9orf72 pathological expansion carriers. Observing the sEVs nano-compartment, we observed increased cathepsin D sEV cargo (ng/sEV) levels in genetic/sporadic FTLD. The diagnostic performance of this biomarker was fairly high (AUC = 0.85). Moreover, sEV and plasma cathepsin D levels were positively correlated with age at onset. In conclusion, our study further emphasizes the common occurrence of endo-lysosomal dysregulation in GRN/C9orf72 and sporadic FTLD.

Knowledge of the stress-induced metabolic alterations in tolerant and sensitive plants is pivotal for identifying interesting traits that improve plant resilience toward unfavorable environmental conditions. This represents a hot topic area of plant science, particularly for crops, due to its implication in food security. Two rice varieties showing dissimilar resistance to salt, Baldo and Vialone Nano, have been studied to investigate the mechanisms underpinning tolerance toward salinity, and these studies have focused on the root system. A detailed analysis of the salt stress-dependent modulation of the redox network is here presented. The different phenotype observed after salt exposure in the two rice varieties is coherent with a differential regulation of cell-cycle progression and cell-death patterns observed at root level. Baldo, the tolerant variety, already showed a highly responsive antioxidative capacity in control conditions. Consistently, stressed Baldo plants showed a different pattern of H 2 O 2 accumulation compared to Vialone Nano. Moreover, glutathione metabolism was finely modulated at transcriptional, post-transcriptional, and post-translational levels in Baldo. These results contribute to highlight the role of ROS and antioxidative pathways as a part of a complex redox network activated in rice toward salt stress.

Tau is a microtubule-associated protein, coded by the MAPT gene, which regulates microtubule (MT) polymerization and dynamics. Due to its key role in neurons, it is a major player in neurodegenerative diseases known as "tauopathies". Since tau has emerged as a multitasking protein with a role in genome stability, it may act both in neurodegeneration and cancer. After demonstrating that tau can be considered as a risk factor for cancer, here we explored the mechanisms linking mutated tau to dysregulation of cancer-relevant processes, by employing lymphoblastoid cell lines (LCL) from patients affected by genetic tauopathy carrying the MAPT P301L mutation and healthy controls (wild-type, wt). In mutated LCL, we found reduced sensitivity to MT perturbation, along with decreased G2/M accumulation and cyclin B1 levels. Furthermore, mutated LCL displayed lower levels of phospho-Chk1 and phospho-Chk2 following hydrogen peroxide-induced oxidative stress, indicating a poorly effective DNA damage checkpoint, as well as reduced basal levels of p53. Such cells also exhibited lower levels of Bax and cleaved caspase-3, and increased levels of Cdc25A, upon oxidative stress, accounting for diminished apoptosis. Overall, these findings point to tau as a key player in biological pathways relevant for cancer, as evidenced by the differential response of mutated and wt cells to MT and DNA perturbation. The modulation of p53 is intriguing given its function as guardian of the genome., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The comprehension of pathogenetic mechanisms in tauopathy-associated neurodegenerative diseases can be improved by the knowledge of the biochemical and biophysical features of mutated tau proteins. Here, we used the full-length, wild-type tau, the V363A and V363I mutated species, associated with pathology, and the P301L mutated tau as a benchmark. Using several techniques, including small-angle X-ray scattering, atomic force microscopy, thioflavin T binding, and electrophoretic separation, we compared their course from intrinsically disordered monomers in solution to early-stage recruitment in complexes and then aggregates of increasing size over long periods up to the asymptotic aggregative behavior of full-length tau proteins. We showed that diversity in the kinetics of recruitment and aggregate structure occurs from the beginning and spreads all over their pathway to very large objects. The different extents of conformational changes and types of molecular assemblies among the proteins were also reflected in their in vitro toxicity; this variation could correlate with physiopathology in humans, considering that the P301L mutation is more aggressive than V363A, especially V363I. This study identified the presence of aggregation intermediates and corroborated the oligomeric hypothesis of tauopathies., (Copyright © 2022. Published by Elsevier B.V.)

Cutting-edge research suggests endosomal/immune dysregulation in GRN / C9orf72 -associated frontotemporal lobar degeneration (FTLD). In this retrospective study, we investigated plasma small extracellular vesicles (sEVs) and complement proteins in 172 subjects (40 Sporadic FTLD, 40 Intermediate/Pathological C9orf72 expansion carriers, and 49 Heterozygous/Homozygous GRN mutation carriers, 43 controls). Plasma sEVs (concentration, size) were analyzed by nanoparticle tracking analysis; plasma and sEVs C1q, C4, C3 proteins were quantified by multiplex assay. We demonstrated that genetic/sporadic FTLD share lower sEV concentrations and higher sEV sizes. The diagnostic performance of the two most predictive variables (sEV concentration/size ratio) was high (AUC = 0.91, sensitivity 85.3%, specificity 81.4%). C1q, C4, and C3 cargo per sEV is increased in genetic and sporadic FTLD. C4 (cargo per sEV, total sEV concentration) is increased in Sporadic FTLD and reduced in GRN + Homozygous, suggesting its specific unbalance compared with Heterozygous cases. C3 plasma level was increased in genetic vs. sporadic FTLD. Looking at complement protein compartmentalization, in control subjects, the C3 and C4 sEV concentrations were roughly half that in respect to those measured in plasma; interestingly, this compartmentalization was altered in different ways in patients. These results suggest sEVs and complement proteins as potential therapeutic targets to mitigate neurodegeneration in FTLD.

Background: Rett syndrome (RTT) is a monogenic X-linked neurodevelopmental disorder characterized by loss-of-function mutations in the MECP2 gene, which lead to structural and functional changes in synapse communication, and impairments of neural activity at the basis of cognitive deficits that progress from an early age. While the restoration of MECP2 in animal models has been shown to rescue some RTT symptoms, gene therapy intervention presents potential side effects, and with gene- and RNA-editing approaches still far from clinical application, strategies focusing on signaling pathways downstream of MeCP2 may provide alternatives for the development of more effective therapies in vivo. Here, we investigate the role of the c-Jun N-terminal kinase (JNK) stress pathway in the pathogenesis of RTT using different animal and cell models and evaluate JNK inhibition as a potential therapeutic approach., Results: We discovered that the c-Jun N-terminal kinase (JNK) stress pathway is activated in Mecp2-knockout, Mecp2-heterozygous mice, and in human MECP2-mutated iPSC neurons. The specific JNK inhibitor, D-JNKI1, promotes recovery of body weight and locomotor impairments in two mouse models of RTT and rescues their dendritic spine alterations. Mecp2-knockout presents intermittent crises of apnea/hypopnea, one of the most invalidating RTT pathological symptoms, and D-JNKI1 powerfully reduces this breathing dysfunction. Importantly, we discovered that also neurons derived from hiPSC-MECP2 mut show JNK activation, high-phosphorylated c-Jun levels, and cell death, which is not observed in the isogenic control wt allele hiPSCs. Treatment with D-JNKI1 inhibits neuronal death induced by MECP2 mutation in hiPSCs mut neurons., Conclusions: As a summary, we found altered JNK signaling in models of RTT and suggest that D-JNKI1 treatment prevents clinical symptoms, with coherent results at the cellular, molecular, and functional levels. This is the first proof of concept that JNK plays a key role in RTT and its specific inhibition offers a new and potential therapeutic tool to tackle RTT., (© 2021. The Author(s).)

Plants are primary resources for oxygen and foods whose production is fundamental for our life. However, diseases and pests may interfere with plant growth and cause a significant reduction of both the quality and quantity of agriculture products. Increasing agricultural productivity is crucial for poverty reduction and food security improvements. For this reason, the 2030 Agenda for Sustainable Development gives a central role to agriculture by promoting a strong technological innovation for advancing sustainable practices at the plant level. To accomplish this aim, recently, wearable sensors and flexible electronics have been extended from humans to plants for measuring elongation, microclimate, and stressing factors that may affect the plant's healthy growth. Unexpectedly, fiber Bragg gratings (FBGs), which are very popular in health monitoring applications ranging from civil infrastructures to the human body, are still overlooked for the agriculture sector. In this work, for the first time, plant wearables based on FBG technology are proposed for the continuous and simultaneous monitoring of plant growth and environmental parameters (i.e., temperature and humidity) in real settings. The promising results demonstrated the feasibility of FBG-based sensors to work in real situations by holding the promise to advance continuous and accurate plant health growth monitoring techniques.

The anti-oxidative activity of plant-derived extracts is well-known and confers health-promoting effects on functional foods and food supplements. Aim of this work is to evaluate the capability of two different assays to predict the real biological antioxidant efficiency. At this purpose, extracts from five different plant-derived matrices and commercial purified phytochemicals were analyzed for their anti-oxidative properties by using well-standardized in vitro chemical method (TEAC) and an ex vivo biological assay. The biological assay, a cellular membrane system obtained from erythrocytes of healthy volunteers, is based on the capability of phytochemicals treatment to prevent membrane lipid peroxidation under oxidative stress by UV-B radiation. Plant extracts naturally rich in phenols with different structure and purified phytochemicals showed different in vitro and ex vivo antioxidant capacities. A high correlation between phenolic contents of the plant-derived extracts and their ability to prevent oxidative injuries in a biological system was found, thus underlying the relevance of this class of metabolites in preventing oxidative stress. On the other hand, a low correlation between the antioxidant capacities was shown between in vitro and ex vivo antioxidant assay. Moreover, data presented in this work show how food complex matrices are more effective in preventing oxidative damages at biological level than pure phytochemicals, even if for these latter, the antioxidant activity was generally higher than that observed for food complex matrices.

Background: Alzheimer's disease (AD) is the most common age-related dementia. Besides its typical presentation with amnestic syndrome at onset, atypical AD cases are being increasingly recognized, often in presenile age., Objectives: To provide an extensive clinical and genetic characterization of six AD patients carrying one or more singular features, including age of onset, atypical phenotype and disease progression rate. By reviewing the pertinent literature and accessing publicly available databases, we aimed to assess the frequency and the significance of the identified genetic variants., Methods: Biomarkers of amyloid-β deposition and neurodegeneration were used to establish the in vivo diagnosis of probable AD, in addition to neurological and neuropsychological evaluation, extensive laboratory assays and neuroradiological data. Considering the presenile onset of the majority of the cases, we hypothesized genetically determined AD and performed extensive genetic analyses by both Sanger sequencing and next generation sequencing (NGS)., Results: We disclosed two known missense variants, one in PSEN1 and the other in PSEN2, and a novel silent variant in PSEN2. Most notably, we identified several additional variants in other dementia-related genes by NGS. Some of them have never been reported in any control or disease databases, representing variants unique to our cases., Conclusions: This work underlines the difficulties in reaching a confident in vivo diagnosis in cases of atypical dementia. Moreover, a wider genetic analysis by NGS approach may prove to be useful in specific cases, especially when the study of the so-far known AD causative genes produces negative or conflicting results.

Class III plant peroxidases (Prxs) are involved in the oxidative polymerization of lignins. Z innia elegans Jacq. Basic peroxidase (ZePrx) has been previously characterized as capable of catalyzing this reaction in vitro and the role in lignin biosynthesis of several of its Arabidopsis thaliana homologous has been previously confirmed. In the present work, ZePrx was overexpressed in Nicotiana tabacum to further characterize its function in planta with particular attention to its involvement in lignin biosynthesis. Since Prxs are known to alter ROS levels by using them as electron acceptor or producing them in their catalytic activity, the impact of this overexpression in redox homeostasis was studied by analyzing the metabolites and enzymes of the ascorbate-glutathione cycle. In relation to the modification induced by ZePrx overexpression in lignin composition and cellular metabolism, the carbohydrate composition of the cell wall as well as overall gene expression through RNA-Seq were analyzed. The obtained results indicate that the overexpression of ZePrx caused an increase in syringyl lignin in cell wall stems, suggesting that ZePrx is relevant for the oxidation of sinapyl alcohol during lignin biosynthesis, coherently with its S-peroxidase nature. The increase in the glucose content of the cell wall and the reduction of the expression of several genes involved in secondary cell wall biosynthesis suggests the occurrence of a possible compensatory response to maintain cell wall properties. The perturbation of cellular redox homeostasis occurring as a consequence of ZePrx overexpression was kept under control by an increase in APX activity and a reduction in ascorbate redox state. In conclusion, our results confirm the role of ZePrx in lignin biosynthesis and highlight that its activity alters cellular pathways putatively aimed at maintaining redox homeostasis., (Copyright © 2020 García-Ulloa, Sanjurjo, Cimini, Encina, Martínez-Rubio, Bouza, Barral, Estévez-Pérez, Novo-Uzal, De Gara and Pomar.)

Progranulin gene (GRN) mutations are among the leading causes of frontotemporal lobar degeneration, a group of neurodegenerative diseases characterized by remarkable clinical heterogeneity. In this article, we report the new GRN 708+4A>T splicing mutation, identified in 2 siblings of a family with several members affected by cognitive, behavioral, and motor disorders. Plasma progranulin dosage and GRN expression analysis, together with in silico prediction studies, supported the pathogenicity of the mutation. Both the patients displayed a clinical syndrome in which language impairment was largely predominant. However, motor speech deficits were the major feature in one case, diagnosed as progressive nonfluent aphasia, whereas marked semantic alterations were present in the other, whose clinical phenotype was in favor of a mixed aphasia. The profile of neuroanatomical alterations from imaging studies was in line with the clinical phenotypes. Therefore, also this novel GRN mutation is associated with haploinsufficiency and phenotypic heterogeneity, which are both typical features of progranulinopathies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Plants are continuously faced with complex environmental conditions which can affect the oxidative metabolism and photosynthetic efficiency, thus leading to the over-production of reactive oxygen species (ROS). Over a certain threshold, ROS can damage DNA. DNA damage, unless repaired, can affect genome stability, thus interfering with cell survival and severely reducing crop productivity. A complex network of pathways involved in DNA damage response (DDR) needs to be activated in order to maintain genome integrity. The expression of specific genes belonging to these pathways can be used as indicators of oxidative DNA damage and effective DNA repair in plants subjected to stress conditions. Managing ROS levels by modulating their production and scavenging systems shifts the role of these compounds from toxic molecules to key messengers involved in plant tolerance acquisition. Oxidative and anti-oxidative signals normally move among the different cell compartments, including the nucleus, cytosol, and organelles. Nuclei are dynamically equipped with different redox systems, such as glutathione (GSH), thiol reductases, and redox regulated transcription factors (TFs). The nuclear redox network participates in the regulation of the DNA metabolism, in terms of transcriptional events, replication, and repair mechanisms. This mainly occurs through redox-dependent regulatory mechanisms comprising redox buffering and post-translational modifications, such as the thiol-disulphide switch, glutathionylation, and S-nitrosylation. The regulatory role of microRNAs (miRNAs) is also emerging for the maintenance of genome stability and the modulation of antioxidative machinery under adverse environmental conditions. In fact, redox systems and DDR pathways can be controlled at a post-transcriptional level by miRNAs. This review reports on the interconnections between the DDR pathways and redox balancing systems. It presents a new dynamic picture by taking into account the shared regulatory mechanism mediated by miRNAs in plant defense responses to stress.

Cyclic AMP plays important roles in different physiological processes, including plant defence responses. However, as little information is known on plant enzymes responsible for cAMP production/degradation, studies of cAMP functions have relied, to date, on non-specific pharmacological approaches. We therefore developed a more reliable approach, producing transgenic Arabidopsis thaliana lines overexpressing the 'cAMP-sponge' (cAS), a genetic tool that specifically buffers cAMP levels. In response to an avirulent strain of Pseudomonas syringae pv. tomato (PstAvrB), cAS plants showed a higher bacterial growth and a reduced hypersensitive cell death in comparison with wild-type (WT) plants. The low cAMP availability after pathogen infection delayed cytosolic calcium elevation, as well as hydrogen peroxide increase and induction of redox systems. The proteomic analysis, performed 24 h post-infection, indicated that a core of 49 proteins was modulated in both genotypes, while 16 and 42 proteins were uniquely modulated in WT and cAS lines, respectively. The involvement of these proteins in the impairment of defence response in cAS plants is discussed in this paper. Moreover, in silico analysis revealed that the promoter regions of the genes coding for proteins uniquely accumulating in WT plants shared the CGCG motif, a target of the calcium-calmodulin-binding transcription factor AtSR1 (Arabidopsis thaliana signal responsive1). Therefore, following pathogen perception, the low free cAMP content, altering timing and levels of defence signals, and likely acting in part through the mis-regulation of AtSR1 activity, affected the speed and strength of the immune response., (© 2019 The Authors The Plant Journal © 2019 John Wiley & Sons Ltd.)

Mutations in the gene encoding DJ-1 are associated with autosomal recessive forms of Parkinson's disease (PD). DJ-1 plays a role in protection from oxidative stress, but how it functions as an "upstream" oxidative stress sensor and whether this relates to PD is still unclear. Intriguingly, DJ-1 may act as an RNA binding protein associating with specific mRNA transcripts in the human brain. Moreover, we previously reported that the yeast DJ-1 homolog Hsp31 localizes to stress granules (SGs) after glucose starvation, suggesting a role for DJ-1 in RNA dynamics. Here, we report that DJ-1 interacts with several SG components in mammalian cells and localizes to SGs, as well as P-bodies, upon induction of either osmotic or oxidative stress. By purifying the mRNA associated with DJ-1 in mammalian cells, we detected several transcripts and found that subpopulations of these localize to SGs after stress, suggesting that DJ-1 may target specific mRNAs to mRNP granules. Notably, we find that DJ-1 associates with SGs arising from N-methyl-D-aspartate (NMDA) excitotoxicity in primary neurons and parkinsonism-inducing toxins in dopaminergic cell cultures. Thus, our results indicate that DJ-1 is associated with cytoplasmic RNA granules arising during stress and neurodegeneration, providing a possible link between DJ-1 and RNA dynamics which may be relevant for PD pathogenesis.

Retrograde pathways occurring between chloroplasts, mitochondria, and the nucleus involve oxidative and antioxidative signals that, working in a synergistic or antagonistic mode, control the expression of specific patterns of genes following stress perception. Increasing evidence also underlines the relevance of mitochondrion-chloroplast-nucleus crosstalk in modulating the whole cellular redox metabolism by a controlled and integrated flux of information. Plants can maintain the acquired tolerance by a stress memory, also operating at the transgenerational level, via epigenetic and miRNA-based mechanisms controlling gene expression. Data discussed in this review strengthen the idea that ROS, redox signals, and shifts in cellular redox balance permeate the signalling network leading to cross-tolerance. The identification of specific ROS/antioxidative signatures leading a plant to different fates under stress is pivotal for identifying strategies to monitor and increase plant fitness in a changing environment. This review provides an update of the plant redox signalling network implicated in stress responses, in particular in cross-tolerance acquisition. The interplay between reactive oxygen species (ROS), ROS-derived signals, and antioxidative pathways is also discussed in terms of plant acclimation to stress in the short and long term.