A mutation in F-actin polymerization factor suppresses the distal arthrogryposis type 5 PIEZO2 pathogenic variant in Caenorhabditis elegans.

The mechanosensitive PIEZO channel family has been linked to over 26 disorders and diseases. Although progress has been made in understanding these channels at the structural and functional levels, the underlying mechanisms of PIEZO-associated diseases remain elusive. In this study, we engineered four PIEZO-based disease models using CRISPR/Cas9 gene editing. We performed an unbiased chemical mutagen-based genetic suppressor screen to identify putative suppressors of a conserved gain-of-function variant pezo-1[R2405P] that in human PIEZO2 causes distal arthrogryposis type 5 (DA5; p. R2718P). Electrophysiological analyses indicate that pezo-1(R2405P) is a gain-of-function allele. Using genomic mapping and whole-genome sequencing approaches, we identified a candidate suppressor allele in the C. elegans gene gex-3. This gene is an ortholog of human NCKAP1 (NCK-associated protein 1), a subunit of the Wiskott-Aldrich syndrome protein (WASP)-verprolin homologous protein (WAVE/SCAR) complex, which regulates F-actin polymerization. Depletion of gex-3 by RNAi, or with the suppressor allele gex-3(av259[L353F]), significantly increased brood size and ovulation rate, as well as alleviating the crushed oocyte phenotype of the pezo-1(R2405P) mutant. Expression of GEX-3 in the soma is required to rescue the brood size defects in pezo-1(R2405P) animals. Actin organization and orientation were disrupted and distorted in the pezo-1 mutants. Mutation of gex-3(L353F) partially alleviated these defects. The identification of gex-3 as a suppressor of the pathogenic variant pezo-1(R2405P) suggests that the PIEZO coordinates with the cytoskeleton regulator to maintain the F-actin network and provides insight into the molecular mechanisms of DA5 and other PIEZO-associated diseases.

Caldendrin Is a Repressor of PIEZO2 Channels and Touch Sensation in Mice.

The sense of touch is crucial for cognitive, emotional, and social development and relies on mechanically activated (MA) ion channels that transduce force into an electrical signal. Despite advances in the molecular characterization of these channels, the physiological factors that control their activity are poorly understood. Here, we used behavioral assays, electrophysiological recordings, and various mouse strains (males and females analyzed separately) to investigate the role of the calmodulin-like Ca2+ sensor, caldendrin, as a key regulator of MA channels and their roles in touch sensation. In mice lacking caldendrin (Cabp1 KO), heightened responses to tactile stimuli correlate with enlarged MA currents with lower mechanical thresholds in dorsal root ganglion neurons (DRGNs). The expression pattern of caldendrin in the DRG parallels that of the major MA channel required for touch sensation, PIEZO2. In transfected cells, caldendrin interacts with and inhibits the activity of PIEZO2 in a manner that requires an alternatively spliced sequence in the N-terminal domain of caldendrin. Moreover, targeted genetic deletion of caldendrin in Piezo2-expressing DRGNs phenocopies the tactile hypersensitivity of complete Cabp1 KO mice. We conclude that caldendrin is an endogenous repressor of PIEZO2 channels and their contributions to touch sensation in DRGNs.

Analysis of sulfide signaling in rice highlights specific drought responses.

Hydrogen sulfide regulates essential plant processes, including adaptation responses to stress situations, and the best characterized mechanism of action of sulfide consists of the posttranslational modification of persulfidation. In this study, we reveal the first persulfidation proteome described in rice including 3443 different persulfidated proteins that participate in a broad range of biological processes and metabolic pathways. In addition, comparative proteomics revealed specific proteins involved in sulfide signaling during drought responses. Several proteins involved in the maintenance of cellular redox homeostasis, the TCA cycle and energy-related pathways, and ion transmembrane transport and cellular water homeostasis, highlighting the aquaporin family, showed the highest differential levels of persulfidation. We revealed that water transport activity is regulated by sulfide which correlates to an increasing level of persulfidation of aquaporins. Our findings emphasize the impact of persulfidation on total ATP levels, fatty acid composition, ROS levels, antioxidant enzymatic activities, and relative water content. Interestingly, the persulfidation role on aquaporin transport activity as an adaptation response in rice differs from the current knowledge in Arabidopsis, which emphasizes the distinct role of sulfide improving rice tolerance to drought.

Implications for driving based on the risk of seizures after ischaemic stroke.

BACKGROUND: In addition to other stroke-related deficits, the risk of seizures may impact driving ability after stroke. METHODS: We analysed data from a multicentre international cohort, including 4452 adults with acute ischaemic stroke and no prior seizures. We calculated the Chance of Occurrence of Seizure in the next Year (COSY) according to the SeLECT2.0 prognostic model. We considered COSY<20% safe for private and <2% for professional driving, aligning with commonly used cut-offs. RESULTS: Seizure risks in the next year were mainly influenced by the baseline risk-stratified according to the SeLECT2.0 score and, to a lesser extent, by the poststroke seizure-free interval (SFI). Those without acute symptomatic seizures (SeLECT2.0 0-6 points) had low COSY (0.7%-11%) immediately after stroke, not requiring an SFI. In stroke survivors with acute symptomatic seizures (SeLECT2.0 3-13 points), COSY after a 3-month SFI ranged from 2% to 92%, showing substantial interindividual variability. Stroke survivors with acute symptomatic status epilepticus (SeLECT2.0 7-13 points) had the highest risk (14%-92%). CONCLUSIONS: Personalised prognostic models, such as SeLECT2.0, may offer better guidance for poststroke driving decisions than generic SFIs. Our findings provide practical tools, including a smartphone-based or web-based application, to assess seizure risks and determine appropriate SFIs for safe driving.

Novel modelling approaches to predict the role of antivirals in reducing influenza transmission.

To aid understanding of the effect of antiviral treatment on population-level influenza transmission, we used a novel pharmacokinetic-viral kinetic transmission model to test the correlation between nasal viral load and infectiousness, and to evaluate the impact that timing of treatment with the antivirals oseltamivir or baloxavir has on influenza transmission. The model was run under three candidate profiles whereby infectiousness was assumed to be proportional to viral titer on a natural-scale, log-scale, or dose-response model. Viral kinetic profiles in the presence and absence of antiviral treatment were compared for each individual (N = 1000 simulated individuals); subsequently, viral transmission mitigation was calculated. The predicted transmission mitigation was greater with earlier administration of antiviral treatment, and with baloxavir versus oseltamivir. When treatment was initiated 12-24 hours post symptom onset, the predicted transmission mitigation was 39.9-56.4% for baloxavir and 26.6-38.3% for oseltamivir depending on the infectiousness profile. When treatment was initiated 36-48 hours post symptom onset, the predicted transmission mitigation decreased to 0.8-28.3% for baloxavir and 0.8-19.9% for oseltamivir. Model estimates were compared with clinical data from the BLOCKSTONE post-exposure prophylaxis study, which indicated the log-scale model for infectiousness best fit the observed data and that baloxavir affords greater reductions in secondary case rates compared with neuraminidase inhibitors. These findings suggest a role for baloxavir and oseltamivir in reducing influenza transmission when treatment is initiated within 48 hours of symptom onset in the index patient.

Epilepsy Care in Latin America and the Caribbean: Overcoming Challenges and Embracing Opportunities.

The burden of epilepsy in the Latin America and the Caribbean (LAC) region causes a profound regional impact on the health care system and significantly contributes to the global epilepsy burden. As in many other resource-limited settings worldwide, health care professionals and patients with epilepsy in LAC countries face profound challenges due to a combination of factors, including high disease prevalence, stigmatization of epilepsy, disparities in access to care, limited resources, substantial treatment gaps, insufficient training opportunities for health care providers, and a diverse patient population with varying needs. This article presents an overview of the epidemiology of epilepsy and discusses the principal obstacles to epilepsy care and key contributors to the epilepsy diagnosis and treatment gap in the LAC region. We conclude by highlighting various initiatives across different LAC countries to improve epilepsy care in marginalized communities, listing strategies to mitigate treatment gaps and facilitate better health care access for patients with epilepsy by enhancing the epilepsy workforce.

Metabolomics of Plasma in XLH Patients with Arterial Hypertension: New Insights into the Underlying Mechanisms.

X-linked hypophosphatemia (XLH) is a rare genetic disorder that increases fibroblast growth factor 23 (FGF23). XLH patients have an elevated risk of early-onset hypertension. The precise factors contributing to hypertension in XLH patients have yet to be identified. A multicenter cross-sectional study of adult patients diagnosed with XLH. Metabolomic analysis was performed using ultra-performance liquid chromatography (UPLC) coupled to a high-resolution mass spectrometer. Twenty subjects were included, of which nine (45%) had hypertension. The median age was 44 years. Out of the total, seven (35%) subjects had a family history of hypertension. No statistically significant differences were found between both groups for nephrocalcinosis or hyperparathyroidism. Those with hypertension exhibited significantly higher levels of creatinine (1.08 ± 0.31 mg/dL vs. 0.78 ± 0.19 mg/dL; p = 0.01) and LDL-C (133.33 ± 21.92 mg/dL vs. 107.27 ± 20.12 mg/dL, p = 0.01). A total of 106 metabolites were identified. Acetylcarnitine (p = 0.03), pyruvate p = (0.04), ethanolamine (p = 0.03), and butyric acid (p = 0.001) were significantly different between both groups. This study is the first to examine the metabolomics of hypertension in patients with XLH. We have identified significant changes in specific metabolites that shed new light on the potential mechanisms of hypertension in XLH patients. These findings could lead to new studies identifying associated biomarkers and developing new diagnostic approaches for XLH patients.

Persulfidation protects from oxidative stress under nonphotorespiratory conditions in Arabidopsis.

Hydrogen sulfide is a signaling molecule in plants that regulates essential biological processes through protein persulfidation. However, little is known about sulfide-mediated regulation in relation to photorespiration. Here, we performed label-free quantitative proteomic analysis and observed a high impact on protein persulfidation levels when plants grown under nonphotorespiratory conditions were transferred to air, with 98.7% of the identified proteins being more persulfidated under suppressed photorespiration. Interestingly, a higher level of reactive oxygen species (ROS) was detected under nonphotorespiratory conditions. Analysis of the effect of sulfide on aspects associated with non- or photorespiratory growth conditions has demonstrated that it protects plants grown under suppressed photorespiration. Thus, sulfide amends the imbalance of carbon/nitrogen and restores ATP levels to concentrations like those of air-grown plants; balances the high level of ROS in plants under nonphotorespiratory conditions to reach a cellular redox state similar to that in air-grown plants; and regulates stomatal closure, to decrease the high guard cell ROS levels and induce stomatal aperture. In this way, sulfide signals the CO2 -dependent stomata movement, in the opposite direction of the established abscisic acid-dependent movement. Our findings suggest that the high persulfidation level under suppressed photorespiration reveals an essential role of sulfide signaling under these conditions.

ß-Cyanoalanine synthase protects mites against Arabidopsis defenses.

Glucosinolates are antiherbivory chemical defense compounds in Arabidopsis (Arabidopsis thaliana). Specialist herbivores that feed on brassicaceous plants have evolved various mechanisms aimed at preventing the formation of toxic isothiocyanates. In contrast, generalist herbivores typically detoxify isothiocyanates through glutathione conjugation upon exposure. Here, we examined the response of an extreme generalist herbivore, the two-spotted spider mite Tetranychus urticae (Koch), to indole glucosinolates. Tetranychus urticae is a composite generalist whose individual populations have a restricted host range but have an ability to rapidly adapt to initially unfavorable plant hosts. Through comparative transcriptomic analysis of mite populations that have differential susceptibilities to Arabidopsis defenses, we identified ß-cyanoalanine synthase of T. urticae (TuCAS), which encodes an enzyme with dual cysteine and ß-cyanoalanine synthase activities. We combined Arabidopsis genetics, chemical complementation and mite reverse genetics to show that TuCAS is required for mite adaptation to Arabidopsis through its ß-cyanoalanine synthase activity. Consistent with the ß-cyanoalanine synthase role in detoxification of hydrogen cyanide (HCN), we discovered that upon mite herbivory, Arabidopsis plants release HCN. We further demonstrated that indole glucosinolates are sufficient for cyanide formation. Overall, our study uncovered Arabidopsis defenses that rely on indole glucosinolate-dependent cyanide for protection against mite herbivory. In response, Arabidopsis-adapted mites utilize the ß-cyanoalanine synthase activity of TuCAS to counter cyanide toxicity, highlighting the mite's ability to activate resistant traits that enable this extreme polyphagous herbivore to exploit cyanogenic host plants.

Old poisons, new signaling molecules: the case of hydrogen cyanide.

The high phenotypic plasticity developed by plants includes rapid responses and adaptations to aggressive or changing environments. To achieve this, they evolved extremely efficient mechanisms of signaling mediated by a wide range of molecules, including small signal molecules. Among them, hydrogen cyanide (HCN) has been largely ignored due to its toxic characteristics. However, not only is it present in living organisms, but it has been shown that it serves several functions in all kingdoms of life. Research using model plants has changed the traditional point of view, and it has been demonstrated that HCN plays a positive role in the plant response to pathogens independently of its toxicity. Indeed, HCN induces a response aimed at protecting the plant from pathogen attack, and the HCN is provided either exogenously (in vitro or by some cyanogenic bacteria species present in the rhizosphere) or endogenously (in reactions involving ethylene, camalexin, or other cyanide-containing compounds). The contribution of different mechanisms to HCN function, including a new post-translational modification of cysteines in proteins, namely S-cyanylation, is discussed here. This work opens up an expanding 'HCN field' of research related to plants and other organisms.

Sulfide promotes tolerance to drought through protein persulfidation in Arabidopsis.

Hydrogen sulfide (H2S) is a signaling molecule that regulates essential plant processes. In this study, the role of H2S during drought was analysed, focusing on the underlying mechanism. Pretreatments with H2S before imposing drought on plants substantially improved the characteristic stressed phenotypes under drought and decreased the levels of typical biochemical stress markers such as anthocyanin, proline, and hydrogen peroxide. H2S also regulated drought-responsive genes and amino acid metabolism, and repressed drought-induced bulk autophagy and protein ubiquitination, demonstrating the protective effects of H2S pretreatment. Quantitative proteomic analysis identified 887 significantly different persulfidated proteins between control and drought stress plants. Bioinformatic analyses of the proteins more persulfidated in drought revealed that the most enriched biological processes were cellular response to oxidative stress and hydrogen peroxide catabolism. Protein degradation, abiotic stress responses, and the phenylpropanoid pathway were also highlighted, suggesting the importance of persulfidation in coping with drought-induced stress. Our findings emphasize the role of H2S as a promoter of enhanced tolerance to drought, enabling plants to respond more rapidly and efficiently. Furthermore, the main role of protein persulfidation in alleviating reactive oxygen species accumulation and balancing redox homeostasis under drought stress is highlighted.

Persulfidation of plant and bacteroid proteins is involved in legume nodule development and senescence.

Legumes establish symbiosis with rhizobia forming nitrogen-fixing nodules. The central role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in nodule biology has been clearly established. Recently, hydrogen sulfide (H2S) and other reactive sulfur species (RSS) have emerged as novel signaling molecules in animals and plants. A major mechanism by which ROS, RNS, and RSS fulfil their signaling role is the post-translational modification of proteins. To identify possible functions of H2S in nodule development and senescence, we used the tag-switch method to quantify changes in the persulfidation profile of common bean (Phaseolus vulgaris) nodules at different developmental stages. Proteomic analyses indicate that persulfidation plays a regulatory role in plant and bacteroid metabolism and senescence. The effect of a H2S donor on nodule functioning and on several proteins involved in ROS and RNS homeostasis was also investigated. Our results using recombinant proteins and nodulated plants support a crosstalk among H2S, ROS and RNS, a protective function of persulfidation on redox-sensitive enzymes, and a beneficial effect of H2S on symbiotic nitrogen fixation. We conclude that the general decrease of persulfidation levels observed in plant proteins of aging nodules is one of the mechanisms that disrupt redox homeostasis leading to senescence.

Role of hydraulic traits in stomatal regulation of transpiration under different vapour pressure deficits across five Mediterranean tree crops.

The differential stomatal regulation of transpiration among plant species in response to water deficit is not fully understood, although several hydraulic traits have been reported to influence it. This knowledge gap is partly due to a lack of direct and concomitant experimental data on transpiration, stomatal conductance, and hydraulic traits. We measured sap flux density (Js), stomatal conductance (gs), and different hydraulic traits in five crop species. Our aim was to contribute to establishing the causal relationship between water consumption and its regulation using a hydraulic trait-based approach. The results showed that the species-specific regulation of Js by gs was overall coordinated with the functional hydraulic traits analysed. Particularly relevant was the negative and significant relationship found between the Huber value (Hv) and its functional analogue ratio between maximum Js and gs (Jsmax/gsmax) which can be understood as a compensation to maintain the hydraulic supply to the leaves. The Hv was also significantly related to the slope of the relationship between gs and Js response to vapour pressure deficit and explained most of its variability, adding up to evidence recognizing Hv as a major trait in plant water relations. Thus, a hydraulic basis for regulation of tree water use should be considered.

Abscisic Acid-Triggered Persulfidation of the Cys Protease ATG4 Mediates Regulation of Autophagy by Sulfide.

Hydrogen sulfide is a signaling molecule that regulates essential processes in plants, such as autophagy. In Arabidopsis (Arabidopsis thaliana), hydrogen sulfide negatively regulates autophagy independently of reactive oxygen species via an unknown mechanism. Comparative and quantitative proteomic analysis was used to detect abscisic acid-triggered persulfidation that reveals a main role in the control of autophagy mediated by the autophagy-related (ATG) Cys protease AtATG4a. This protease undergoes specific persulfidation of Cys170 that is a part of the characteristic catalytic Cys-His-Asp triad of Cys proteases. Regulation of the ATG4 activity by persulfidation was tested in a heterologous assay using the Chlamydomonas reinhardtii CrATG8 protein as a substrate. Sulfide significantly and reversibly inactivates AtATG4a. The biological significance of the reversible inhibition of the ATG4 by sulfide is supported by the results obtained in Arabidopsis leaves under basal and autophagy-activating conditions. A significant increase in the overall ATG4 proteolytic activity in Arabidopsis was detected under nitrogen starvation and osmotic stress and can be inhibited by sulfide. Therefore, the data strongly suggest that the negative regulation of autophagy by sulfide is mediated by specific persulfidation of the ATG4 protease.

Persulfidation-based Modification of Cysteine Desulfhydrase and the NADPH Oxidase RBOHD Controls Guard Cell Abscisic Acid Signaling.

Hydrogen sulfide (H2S) is a gaseous signaling molecule that regulates diverse cellular signaling pathways through persulfidation, which involves the post-translational modification of specific Cys residues to form persulfides. However, the mechanisms that underlie this important redox-based modification remain poorly understood in higher plants. We have, therefore, analyzed how protein persulfidation acts as a specific and reversible signaling mechanism during the abscisic acid (ABA) response in Arabidopsis (Arabidopsis thaliana). Here we show that ABA stimulates the persulfidation of l-CYSTEINE DESULFHYDRASE1, an important endogenous H2S enzyme, at Cys44 and Cys205 in a redox-dependent manner. Moreover, sustainable H2S accumulation drives persulfidation of the NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG PROTEIN D (RBOHD) at Cys825 and Cys890, enhancing its ability to produce reactive oxygen species. Physiologically, s-persulfidation-induced RBOHD activity is relevant to ABA-induced stomatal closure. Together, these processes form a negative feedback loop that fine-tunes guard cell redox homeostasis and ABA signaling. These findings not only expand our current knowledge of H2S function in the context of guard cell ABA signaling, but also demonstrate the presence of a rapid signal integration mechanism involving specific and reversible redox-based post-translational modifications that occur in response to changing environmental conditions.

Evaluation of epilepsy surgery scope and training in Latin America.

INTRODUCTION: To describe the variety of surgical epilepsy procedures offered in Latin America and characterize the training in surgical management for epilepsy and neurophysiology fellows. MATERIALS & METHODS: A 15-question survey was sent to Spanish-speaking epilepsy specialists in Latin America (members of the International Consortium in Epilepsy Surgery Education) to characterize their epilepsy surgery practices and formal training programs when present, including fellowship program characteristics, trainee involvement, and assessment of trainee performance. Epilepsy surgery procedures included resective/ablative interventions and neuromodulation therapies approved for drug-resistant epilepsy. Associations between categorical variables were evaluated using the Fisher Exact test. RESULTS: There were 42 responses from a total of 57 survey recipients (73% response rate). Most surgical programs performed either 1 to 10 procedures (36%) or 11 to 30 procedures (31%) per year. Most centers (88%) performed resective procedures, while none of the surveyed institutions performed laser ablations. Most of the centers performing intracranial EEG (88%) and advanced neuromodulation (93%) were in South America. Centers with formal fellowship training programs were more likely to perform intracranial EEG procedures compared to centers without fellows (92% vs 48%, respectively, OR = 12.2 [95% CI 1.45-583], p = 0.007). DISCUSSION: There is significant variability in surgical procedures performed across epilepsy centers in a Latin American educational consortium. Advanced surgical diagnostic procedures and interventions are performed in a fair number of surveyed institutions. Strategies to enhance access to epilepsy surgery procedures and facilitate formal training in surgical management are necessary.

Removal of heavy metals from mine tailings by in-situ bioleaching coupled to electrokinetics.

This work utilizes a combined biological-electrochemical technique for the in-situ removal of metals from polluted mine tailings. As the main novelty point it is proposed to use electrokinetics (EK) for the in-situ activation of a bioleaching mechanism into the tailings, in order to promote biological dissolution of metal sulphides (Step 1), and for the subsequent removal of leached metals by EK transport out of the tailings (Step 2). Mine tailings were collected from an abandoned Pb/Zn mine located in central-southern Spain. EK-bioleaching experiments were performed under batch mode using a lab scale EK cell. A mixed microbial culture of autochthonous acidophilic bacteria grown from the tailings was used. Direct current with polarity reversal vs alternate current was evaluated in Step 1. In turn, different biological strategies were used: biostimulation, bioaugmentation and the abiotic reference test (EK alone). It was observed that bioleaching activation was very low during Step 1, because it was difficult to maintain acidic pH in the whole soil, but then it worked correctly during Step 2. It was confirmed that microorganisms successfully contributed to the in-situ solubilization of the metal sulphides as final metal removal rates were improved compared to the conventional abiotic EK (best increases of around 40% for Cu, 162% for Pb, 18% for Zn, 13% for Mn, 40% for Ni and 15% for Cr). Alternate current seemed to be the best option. The tailings concentrations of Fe, Al, Cu, Mn, Ni and Pb after treatment comply with regulations, but Pb, Cd and Zn concentrations exceed the maximum values. From the data obtained in this work it has been observed that EK-bioleaching could be feasible, but some upgrades and future work must be done in order to optimize experimental conditions, especially the control of soil pH in acidic values.

Indoor Content Delivery Solution for a Museum Based on BLE Beacons.

The digital transformation advancement enables multiple areas to provide modern services to their users. Culture is one of the areas that can benefit from these advances, more specifically museums, by presenting many benefits and the most emergent technologies to the visitors. This paper presents an indoor location system and content delivery solution, based on Bluetooth Low Energy Beacons, that enable visitors to walk freely inside the museum and receive augmented reality content based on the acquired position, which is done using the Received Signal Strength Indicator (RSSI). The solution presented in this paper was created for the Foz Côa Museum in Portugal and was tested in the real environment. A detailed study was carried out to analyze the RSSI under four different scenarios, and detection tests were carried out that allowed us to measure the accuracy of the room identification, which is needed for proper content delivery. Of the 89 positions tested in the four scenarios, 70% of the received signals were correctly received throughout the entire duration of the tests, 20% were received in an intermittent way, 4% were never detected and 6% of unwanted beacons were detected. The signal detection is fundamental for the correct room identification, which was performed with 96% accuracy. Thus, we verified that this technology is suitable for the proposed solution.

Regulation of V-ATPase by Jasmonic Acid: Possible Role of Persulfidation.

Vacuolar H+-translocating ATPase (V-ATPase) is a proton pump crucial for plant growth and survival. For this reason, its activity is tightly regulated, and various factors, such as signaling molecules and phytohormones, may be involved in this process. The aim of this study was to explain the role of jasmonic acid (JA) in the signaling pathways responsible for the regulation of V-ATPase in cucumber roots and its relationship with other regulators of this pump, i.e., H2S and H2O2. We analyzed several aspects of the JA action on the enzyme, including transcriptional regulation, modulation of protein levels, and persulfidation of selected V-ATPase subunits as an oxidative posttranslational modification induced by H2S. Our results indicated that JA functions as a repressor of V-ATPase, and its action is related to a decrease in the protein amount of the A and B subunits, the induction of oxidative stress, and the downregulation of the E subunit persulfidation. We suggest that both H2S and H2O2 may be downstream components of JA-dependent negative proton pump regulation. The comparison of signaling pathways induced by two negative regulators of the pump, JA and cadmium, revealed that multiple pathways are involved in the V-ATPase downregulation in cucumber roots.

Mexican Colorectal Cancer Research Consortium (MEX-CCRC): Etiology, Diagnosis/Prognosis, and Innovative Therapies.

In 2013, recognizing that Colorectal Cancer (CRC) is the second leading cause of death by cancer worldwide and that it was a neglected disease increasing rapidly in Mexico, the community of researchers at the Biomedicine Research Unit of the Facultad de Estudios Superiores Iztacala from the Universidad Nacional Autónoma de México (UNAM) established an intramural consortium that involves a multidisciplinary group of researchers, technicians, and postgraduate students to contribute to the understanding of this pathology in Mexico. This article is about the work developed by the Mexican Colorectal Cancer Research Consortium (MEX-CCRC): how the Consortium was created, its members, and its short- and long-term goals. Moreover, it is a narrative of the accomplishments of this project. Finally, we reflect on possible strategies against CRC in Mexico and contrast all the data presented with another international strategy to prevent and treat CRC. We believe that the Consortium's characteristics must be maintained to initiate a national strategy, and the reported data could be useful to establish future collaborations with other countries in Latin America and the world.