Plant virus evolution under strong drought conditions results in a transition from parasitism to mutualism.

Environmental conditions are an important factor driving pathogens' evolution. Here, we explore the effects of drought stress in plant virus evolution. We evolved turnip mosaic potyvirus in well-watered and drought conditions in Arabidopsis thaliana accessions that differ in their response to virus infection. Virus adaptation occurred in all accessions independently of watering status. Drought-evolved viruses conferred a significantly higher drought tolerance to infected plants. By contrast, nonsignificant increases in tolerance were observed in plants infected with viruses evolved under standard watering. The magnitude of this effect was dependent on the plant accessions. Differences in tolerance were correlated to alterations in the expression of host genes, some involved in regulation of the circadian clock, as well as in deep changes in the balance of phytohormones regulating defense and growth signaling pathways. Our results show that viruses can promote host survival in situations of abiotic stress, with the magnitude of such benefit being a selectable trait.

APOE genotype, hippocampal volume, and cognitive reserve predict improvement by cognitive training in older adults without dementia: a randomized controlled trial.

Cognitive training (CT) programs aim to improve cognitive performance and impede its decline. Thus, defining the characteristics of individuals who can benefit from these interventions is essential. Our objectives were to assess if the cognitive reserve (CR), APOE genotype (e4 carriers/non-carriers) and/or hippocampal volume might predict the effectiveness of a CT program. Participants were older adults without dementia (n = 226), randomized into parallel experimental and control groups. The assessment consisted of a neuropsychological protocol and additional data regarding total intracranial, gray matter, left/right hippocampus volume; APOE genotype; and Cognitive Reserve (CR). The intervention involved multifactorial CT (30 sessions, 90 min each), with an evaluation pre- and post-training (at six months); the control group simply following the center's routine activities. The primary outcome measures were the change in cognitive performance and the predictors of change. The results show that APOE-e4 non-carriers (79.1%) with a larger left hippocampal volume achieved better gains in semantic verbal fluency (R2 = .19). Subjects with a larger CR and a greater gray matter volume better improved their processing speed (R2 = .18). Age was correlated with the improvement in executive functions, such that older age predicts less improvement (R2 = .07). Subjects with a larger left hippocampal volume achieved more significant gains in general cognitive performance (R2 = .087). In conclusion, besides the program itself, the effectiveness of CT depends on age, biological factors like genotype and brain volume, and CR. Thus, to achieve better results through a CT, it is essential to consider the different characteristics of the participants, including genetic factors.Trial registration: Trial retrospectively registered on January 29th, 2020-(ClinicalTrials.gov -NCT04245579).

Multiple bHLH/MYB-based protein complexes regulate proanthocyanidin biosynthesis in the herbage of Lotus spp.

MAIN CONCLUSION: The complexes involving MYBPA2, TT2b, and TT8 proteins are the critical regulators of ANR and LAR genes to promote the biosynthesis of proanthocyanidins in the leaves of Lotus spp. The environmental impact and health of ruminants fed with forage legumes depend on the herbage's concentration and structure of proanthocyanidins (PAs). Unfortunately, the primary forage legumes (alfalfa and clover) do not contain substantial levels of PAs. No significant progress has been made to induce PAs to agronomically valuable levels in their edible organs by biotechnological approaches thus far. Building this trait requires a profound knowledge of PA regulators and their interplay in species naturally committed to accumulating these metabolites in the target organs. Against this background, we compared the shoot transcriptomes of two inter-fertile Lotus species, namely Lotus tenuis and Lotus corniculatus, polymorphic for this trait, to search for differentially expressed MYB and bHLH genes. We then tested the expression of the above-reported regulators in L. tenuis x L. corniculatus interspecific hybrids, several Lotus spp., and different L. corniculatus organs with contrasting PA levels. We identified a novel MYB activator and MYB-bHLH-based complexes that, when expressed in Nicotiana benthamiana, trans-activated the promoters of L. corniculatus anthocyanidin reductase and leucoanthocyanidin reductase 1 genes. The last are the two critical structural genes for the biosynthesis of PAs in Lotus spp. Competition between MYB activators for the transactivation of these promoters also emerged. Overall, by employing Lotus as a model genus, we refined the transcriptional network underlying PA biosynthesis in the herbage of legumes. These findings are crucial to engineering this trait in pasture legumes.

A genetic approach reveals different modes of action of prefoldins.

The prefoldin complex (PFDc) was identified in humans as a co-chaperone of the cytosolic chaperonin T-COMPLEX PROTEIN RING COMPLEX (TRiC)/CHAPERONIN CONTAINING TCP-1 (CCT). PFDc is conserved in eukaryotes and is composed of subunits PFD1-6, and PFDc-TRiC/CCT folds actin and tubulins. PFDs also participate in a wide range of cellular processes, both in the cytoplasm and in the nucleus, and their malfunction causes developmental alterations and disease in animals and altered growth and environmental responses in yeast and plants. Genetic analyses in yeast indicate that not all of their functions require the canonical complex. The lack of systematic genetic analyses in plants and animals, however, makes it difficult to discern whether PFDs participate in a process as the canonical complex or in alternative configurations, which is necessary to understand their mode of action. To tackle this question, and on the premise that the canonical complex cannot be formed if one subunit is missing, we generated an Arabidopsis (Arabidopsis thaliana) mutant deficient in the six PFDs and compared various growth and environmental responses with those of the individual mutants. In this way, we demonstrate that the PFDc is required for seed germination, to delay flowering, or to respond to high salt stress or low temperature, whereas at least two PFDs redundantly attenuate the response to osmotic stress. A coexpression analysis of differentially expressed genes in the sextuple mutant identified several transcription factors, including ABA INSENSITIVE 5 (ABI5) and PHYTOCHROME-INTERACTING FACTOR 4, acting downstream of PFDs. Furthermore, the transcriptomic analysis allowed assigning additional roles for PFDs, for instance, in response to higher temperature.

Prefoldins contribute to maintaining the levels of the spliceosome LSM2-8 complex through Hsp90 in Arabidopsis.

Although originally identified as the components of the complex aiding the cytosolic chaperonin CCT in the folding of actins and tubulins in the cytosol, prefoldins (PFDs) are emerging as novel regulators influencing gene expression in the nucleus. Work conducted mainly in yeast and animals showed that PFDs act as transcriptional regulators and participate in the nuclear proteostasis. To investigate new functions of PFDs, we performed a co-expression analysis in Arabidopsis thaliana. Results revealed co-expression between PFD and the Sm-like (LSM) genes, which encode the LSM2-8 spliceosome core complex, in this model organism. Here, we show that PFDs interact with and are required to maintain adequate levels of the LSM2-8 complex. Our data indicate that levels of the LSM8 protein, which defines and confers the functional specificity of the complex, are reduced in pfd mutants and in response to the Hsp90 inhibitor geldanamycin. We provide biochemical evidence showing that LSM8 is a client of Hsp90 and that PFD4 mediates the interaction between both proteins. Consistent with our results and with the role of the LSM2-8 complex in splicing through the stabilization of the U6 snRNA, pfd mutants showed reduced levels of this snRNA and altered pre-mRNA splicing patterns.

Genetic Predictors of Change in Episodic Verbal Memory by Cognitive Intervention: ACT, PICALM, BDNF, NRG1, APOE Genes and Their Interactions in Situations of Cognitive Demand.

BACKGROUND: Cognitive interventions (CIs) in the elderly are activities that seek to improve cognitive performance and delay its deterioration. Our objectives were to study potential genetic predictors of how a CI program may influence immediate and delayed episodic verbal memory (EVM). METHODS: 162 participants were elderly individuals without dementia who were randomized into parallel control and experimental groups. Participants underwent genetic testing to analyze the PICALM, ACT, NRG1, BDNF and APOE genes. We performed a broad neuropsychological assessment before and 6 months after the CI. The CI involved multifactorial training (30 sessions). The control group undertook the centre's standard activities. The main outcome measures were the genotype studied as a predictor of post-intervention changes in EVM. RESULTS: We found the CI was associated with improvements in several cognitive functions, including immediate and delayed EVM. While no individual gene was associated with any such change, the interaction between PICALM/ACT (p = 0.008; Eta2 = 0.23) and PICALM/NRG1 (p = 0.029; Eta2 = 0.19) was associated with improved immediate EVM, and the NRG1/BDNF interaction was associated with improved delayed EVM (p = 0.009; Eta2 = 0.21). The APOEε4 genotype was not associated with any change in EVM. CONCLUSIONS: Our study shows that the participants' genotype can have an impact on the results of CIs. Cognitive stress may stimulate the interaction of various genes and as such, different types of CI should be established for distinct groups of people taking into account the individual's characteristics, like genotype, to improve the results of this type of health prevention and promotion activity.

A Bacterial Endophyte from Apoplast Fluids Protects Canola Plants from Different Phytopathogens via Antibiosis and Induction of Host Resistance.

Endophytic bacteria colonize inner plant tissues and thrive at the apoplast, which is considered its main reservoir. Because this niche is the place where the main molecular events take place between beneficial and pathogenic microorganisms, the aim of this work was to characterize culturable endophytic bacteria from apoplastic fluids obtained from field-grown canola leaves and analyze their potential for biological control of diseases caused by Xanthomonas campestris, Sclerotinia sclerotiorum, and Leptosphaeria maculans. Dual-culture analysis indicated that three isolates (Apo8, Apo11, and Apo12) were able to inhibit the growth of all three phytopathogens. Sequencing of the 16S ribosomal RNA and rpoD genes of these isolates revealed that they are closely related to Pseudomonas viridiflava. One of the isolates, Apo11, was able to diminish the propagation of X. campestris in whole-plant assays. At the same time, Apo11 inoculation reduced the necrotic lesions provoked by S. sclerotiorum on canola leaves. This protective effect might be due to the induction of resistance in the host mediated by salicylic and jasmonic acid signaling pathways or the production of compounds with antimicrobial activity. At the same time, Apo11 inoculation promoted canola plant growth. Thus, the isolate characterized in this work has several desirable characteristics, which make it a potential candidate for the formulation of biotechnological products to control plant diseases or promote plant growth.

Characterization of the responses to saline stress in the symbiotic green microalga Trebouxia sp. TR9.

MAIN CONCLUSION: For the first time we provide a study on the physiological, ultrastructural and molecular effects of salt stress on a terrestrial symbiotic green microalga, Trebouxia sp. TR9. Although tolerance to saline conditions has been thoroughly studied in plants and, to an extent, free-living microalgae, scientific data regarding salt stress on symbiotic lichen microalgae is scarce to non-existent. Since lichen phycobionts are capable of enduring harsh, restrictive and rapidly changing environments, it is interesting to study the metabolic machinery operating under these extreme conditions. We aim to determine the effects of prolonged exposure to high salt concentrations on the symbiotic phycobiont Trebouxia sp. TR9, isolated from the lichen Ramalina farinacea. Our results suggest that, when this alga is confronted with extreme saline conditions, the cellular structures are affected to an extent, with limited chlorophyll content loss and photosynthetic activity remaining after 72 h of exposure to 5 M NaCl. Furthermore, this organism displays a rather different molecular response compared to land plants and free-living halophile microalgae, with no noticeable increase in ABA levels and ABA-related gene expression until the external NaCl concentration is raised to 3 M NaCl. Despite this, the ABA transduction pathway seems functional, since the ABA-related genes tested are responsive to exogenous ABA. These observations could suggest that this symbiotic green alga may have developed alternative molecular pathways to cope with highly saline environments.

Cytotaxonomic study of the Chilean endemic complex Alstroemeria magnifica Herb. (Alstroemeriaceae).

Alstroemeria L. (Alstroemeriaceae) represents one of the most diverse genera of vascular plants in Chile. It contains approximately 54 taxa, 40 of which are endemic. The "complex" Alstroemeria magnifica is endemic to Chile, and it comprises four varieties: A. magnifica var. magenta, A. magnifica var. magnifica, A. magnifica var. sierrae, and A. magnifica var. tofoensis. It is distributed from Coquimbo to the Valparaíso Region. We analyzed karyotypes of 10 populations along its natural distribution. All the populations presented an asymmetric karyotype, with 2n = 16 chromosomes but with three different karyotypic formulae. Alstroemeria magnifica var. magnifica and A. magnifica var. sierrae presented the same karyotypic fomula, and A. magnifica var. magenta, and A. magnifica var. tofoensis each had a different formula. The scatter plot among CVCL vs. MCA shows different groupings between populations of the four varieties. Based on the results, it is possible to consider raising Alstroemeria magnifica var. magenta to species level (A. magenta) and A. magnifica var. tofoensis to subspecies level (A. magnifica subsp. tofoensis); A. magnifica var. magnifica and A. magnifica var. sierrae should each remain as varieties. Nevertheless, these taxonomic changes should be considered tentative, as additional sources of evidence become available.

Polyamine oxidase 5 loss-of-function mutations in Arabidopsis thaliana trigger metabolic and transcriptional reprogramming and promote salt stress tolerance.

The family of polyamine oxidases (PAO) in Arabidopsis (AtPAO1-5) mediates polyamine (PA) back-conversion, which reverses the PA biosynthetic pathway from spermine and its structural isomer thermospermine (tSpm) into spermidine and then putrescine. Here, we have studied the involvement of PA back-conversion in Arabidopsis salinity tolerance. AtPAO5 is the Arabidopsis PAO gene member most transcriptionally induced by salt stress. Two independent loss-of-function mutants (atpao5-2 and atpao5-3) were found to exhibit constitutively higher tSpm levels, with associated increased salt tolerance. Using global transcriptional and metabolomic analyses, the underlying mechanisms were studied. Stimulation of abscisic acid and jasmonate (JA) biosynthesis and accumulation of important compatible solutes, such as sugars, polyols and proline, as well as TCA cycle intermediates were observed in atpao5 mutants under salt stress. Expression analyses indicate that tSpm modulates the transcript levels of several target genes, including many involved in the biosynthesis and signalling of JA, some of which are already known to promote salinity tolerance. Transcriptional modulation by tSpm is isomer-dependent, thus demonstrating the specificity of this response. Overall, we conclude that tSpm triggers metabolic and transcriptional reprogramming that promotes salt stress tolerance in Arabidopsis.

Lotus tenuis x L. corniculatus interspecific hybridization as a means to breed bloat-safe pastures and gain insight into the genetic control of proanthocyanidin biosynthesis in legumes.

BACKGROUND: Proanthocyanidins (PAs) are secondary metabolites that strongly affect plant quality traits. The concentration and the structure of these metabolites influence the palatability and nutritional value of forage legumes. Hence, modulating PAs in the leaves of forage legumes is of paramount relevance for forage breeders worldwide. The lack of genetic variation in the leaf PA trait within the most important forage species and the difficulties in engineering this pathway via the ectopic expression of regulatory genes, prompted us to pursue alternative strategies to enhance this trait in forage legumes of agronomic interest. The Lotus genus includes forage species which accumulate PAs in edible organs and can thus be used as potential donor parents in breeding programs. RESULTS: We recovered a wild, diploid and PA-rich population of L. corniculatus and crossed with L. tenuis. The former grows in an alkaline-salty area in Spain while the latter is a diploid species, grown extensively in South American pastures, which does not accumulate PAs in the herbage. The resulting interspecific hybrids displayed several traits of outstanding agronomic relevance such as rhizome production, PA levels in edible tissues sufficient to prevent ruminal bloating (around 5 mg of PAs/g DW), biomass production similar to the cultivated parent and potential for adaptability to marginal lands. We show that PA levels correlate with expression levels of the R2R3MYB transcription factor TT2 and, in turn, with those of the key structural genes of the epicatechin and catechin biosynthetic pathways leading to PA biosynthesis. CONCLUSIONS: The L. tenuis x L. corniculatus hybrids, reported herein, represent the first example of the introgression of the PA trait in forage legumes to levels known to provide nutritional and health benefits to ruminants. Apart from PAs, the hybrids have additional traits which may prove useful to breed forage legumes with increased persistence and adaptability to marginal conditions. Finally, our study suggests the hybrids and their progeny are an invaluable tool to gain a leap forward in our understanding of the genetic control of PA biosynthesis and tolerance to stresses in legumes.

Social Loneliness in Older Adults with Mild Cognitive Impairment: Predictive Factors and Associated Clinical Characteristics.

BACKGROUND: Loneliness and social isolation are considered public health problems among older individuals. In addition, both increase the risk of developing cognitive impairment and dementia. The Social Loneliness construct has been proposed to refer to these harmful social interaction-related factors. OBJECTIVE: To define the risk factors of Social Loneliness in individuals with mild cognitive impairment (MCI) and to analyze cognitive, emotional, and functional differences according to the participant's degree of Social Loneliness. METHODS: Through convenience sampling, 105 participants over 60 diagnosed with MCI were selected. The evaluation consisted of anamnesis and a comprehensive neuropsychological examination. The ESTE-II questionnaire was used to assess Social Loneliness and its three factors: perceived social support, social participation, and use of communication technologies. Personality was measured with the NEO-FFI questionnaire. RESULTS: The predictors of the Social Loneliness factors were as follows; 1) perceived social support (R2 = 0.33): Neuroticism (ß= 0.353), depression (ß= 0.205), and perceived health (ß= 0.133); 2) social participation (R2 = 0.24): Conscientiousness (ß= -0.344) and Extraversion (ß= -0.263); 3) use of communication technologies (R2 = 0.44): age (ß= 0.409), type of cohabitation (ß= 0.331), cognitive reserve (ß= -0.303), and Conscientiousness (ß= -0.247); all p < 0.05. The participants with a higher degree of Social Loneliness showed more depressive symptoms (R2 = 0.133), more memory complaints (R2 = 0.086), worse perceived health (R2 = 0.147), lower attentional performance/processing speed (R2 = 0.094), and more naming difficulties (R2 = 0.132); all p < 0.05. CONCLUSIONS: This research represents an advance in detecting individuals with MCI and an increased risk of developing Social Loneliness, which influences the configuration of the clinical profile of MCI.

Myco-Phycobiont Interactions within the "Ramalina farinacea Group": A Geographical Survey over Europe and Macaronesia.

Ramalina farinacea is a widely distributed epiphytic lichen from the Macaronesian archipelagos to Mediterranean and Boreal Europe. Previous studies have indicated a specific association between R. farinacea and Trebouxia microalgae species. Here, we examined the symbiotic interactions in this lichen and its closest allies (the so-called "R. farinacea group") across ten biogeographic subregions, spanning diverse macroclimates, analyzing the climatic niche of the primary phycobionts, and discussing the specificity of these associations across the studied area. The most common phycobionts in the "R. farinacea group" were T. jamesii and T. lynnae, which showed a preference for continentality and insularity, respectively. The Canarian endemic R. alisiosae associated exclusively with T. lynnae, while the other Ramalina mycobionts interacted with both microalgae. The two phycobionts exhibited extensive niche overlap in an area encompassing Mediterranean, temperate Europe, and Macaronesian localities. However, T. jamesii occurred in more diverse climate types, whereas T. lynnae preferred warmer and more humid climates, often close to the sea, which could be related to its tolerance to salinity. With the geographical perspective gained in this study, it was possible to show how the association with different phycobionts may shape the ecological adaptation of lichen symbioses.

Predictive factors and risk and protection groups for loneliness in older adults: a population-based study.

BACKGROUND: Loneliness is considered a public health problem, particularly among older adults. Although risk factors for loneliness have been studied extensively, fewer studies have focused on the protected and risk groups that these factors configure. Our objective is to analyze the variables and latent factors that predict loneliness in older adults and that enable risk and protected groups to be configured. METHODS: We employed an epidemiological, cross-sectional survey that was carried out on a random sample of 2060 people over 65 years extracted from the census. A structured telephone interview was used to assess mental and physical health, habits, quality of life, and loneliness, applying the COOP-Wonca, Goldberg General Health (GHQ-12), and Barber Questionnaires. RESULTS: Predictors of loneliness were: mental health, living alone, quality of life, depressive symptoms, low educational level, and some deficiency situations such as having no one to turn to for help. The factors extracted (Factorial Analysis) were: a subjective experience of poor health, objective isolation, and psychological isolation. We established at risk and protected groups ("Decision Tree" procedure), and loneliness was referred to by 73.2% of the people living alone and with poor mental health and quality of life (risk group). By contrast, only 0.8% of people living with others, with good mental health and good quality of life felt loneliness (protected group). CONCLUSION: In a well-developed city, subjective and objective factors are associated with loneliness. These factors, especially those associated with at risk or protected groups, must be considered to develop strategies that address loneliness.

The Memory Failures of Everyday (MFE) test: normative data in adults.

UNLABELLED: One approach to the study of everyday memory failures is to use multiple-item questionnaires. The Memory Failures of Everyday (MFE) test is one of the most frequently used in Spain. Our objective is to provide normative data from the MFE in a sample of healthy, Spanish, adult participants for use in clinical practice. The sample consists of 647 employees at a large company ranging in age from 19-64 years-old. Everyday memory failures were evaluated by means of the MFE with the following response format: 0-2 (0 = never or rarely; 1 = occasionally, sometimes; 2 = frequently, often). RESULTS: Mean MFE = 15.25 (SD = 7.50), range 0-40. Correlation with age: .133 (p = .001); and with years of education: - .059 (n.s.). A constant increase in MFE was not observed across age groups (F = 4, 59; p = .003, eta2 = .02), but differences were revealed between the 19-29 and 40-49 age groups; no differences were observed between the remaining age groups. Only slight differences between men and women occurred, the women's mean being slightly higher than the men's, but the confidence intervals overlapped (F = 5, 71; p = .017, eta2 = .01). These results indicate that age, years of education, and sex had no significant effects. In light of the above, the sample was viewed as a whole when computing the percentiles reported here.

The memory failures of everyday questionnaire (MFE): internal consistency and reliability.

The Memory Failures of Everyday Questionnaire (MFE) is one of the most widely-used instruments to assess memory failures in daily life. The original scale has nine response options, making it difficult to apply; we created a three-point scale (0-1-2) with response choices that make it easier to administer. We examined the two versions' equivalence in a sample of 193 participants between 19 and 64 years of age. The test-retest reliability and internal consistency of the version we propose were also computed in a sample of 113 people. Several indicators attest to the two forms' equivalence: the correlation between the items' means (r = .94; p < .001) and the order of the items' frequencies (r = .92; p < .001). However, the correlation between global scores on the two forms was not very high (r = .67; p < .001). The results indicate this new version has adequate reliability and internal consistency (r(xx) = .83; p < .001; alpha = .83; p < .001) equivalent to those of the MFE 1-9. The MFE 0-2 provides a brief, simple evaluation, so we recommend it for use in clinical practice as well as research.

Metabolic Profiling and Metabolite Correlation Network Analysis Reveal That Fusarium solani Induces Differential Metabolic Responses in Lotus japonicus and Lotus tenuis against Severe Phosphate Starvation.

Root fungal endophytes are essential mediators of plant nutrition under mild stress conditions. However, variations in the rhizosphere environment, such as nutrient depletion, could result in a stressful situation for both partners, shifting mutualistic to nonconvenient interactions. Mycorrhizal fungi and dark septate endophytes (DSEs) have demonstrated their ability to facilitate phosphate (Pi) acquisition. However, few studies have investigated other plant-fungal interactions that take place in the root environment with regard to phosphate nutrition. In the present research work, we aimed to analyze the effect of extreme Pi starvation and the fungal endophyte Fusarium solani on the model Lotus japonicus and the crop L. tenuis. We conducted metabolomics analysis based on gas chromatography-mass spectrometry (GC-MS) on plant tissues under optimal conditions, severe Pi starvation and F.solani presence. By combining statistical and correlation network analysis strategies, we demonstrated the differential outcomes of the two plant species against the combination of treatments. The combination of nutritional stress and Fusarium presence activated significant modifications in the metabolism of L. japonicus affecting the levels of sugars, polyols and some amino acids. Our results display potential markers for further inspection of the factors related to plant nutrition and plant-fungal interactions.

Polyamines: molecules with regulatory functions in plant abiotic stress tolerance.

Early studies on plant polyamine research pointed to their involvement in responses to different environmental stresses. During the last few years, genetic, transcriptomic and metabolomic approaches have unravelled key functions of different polyamines in the regulation of abiotic stress tolerance. Nevertheless, the precise molecular mechanism(s) by which polyamines control plant responses to stress stimuli are largely unknown. Recent studies indicate that polyamine signalling is involved in direct interactions with different metabolic routes and intricate hormonal cross-talks. Here we discuss the integration of polyamines with other metabolic pathways by focusing on molecular mechanisms of their action in abiotic stress tolerance. Recent advances in the cross talk between polyamines and abscisic acid are discussed and integrated with processes of reactive oxygen species (ROS) signalling, generation of nitric oxide, modulation of ion channel activities and Ca(2+) homeostasis, amongst others.

Converting drugs into gelators: supramolecular hydrogels from N-acetyl-L-cysteine and coinage-metal salts.

Here we present the concept of metallophilic hydrogels, supramolecular systems in which the gelator species are metal-thiolates that self-assemble through metallophilic attractions. The principle is applied for a small drug, the mucolytic agent N-acetyl-l-cysteine (NAC), which readily forms hydrogels in the presence of Au(iii), Ag(i) and Cu(ii) salts. The resulting transparent hydrogels present pH induced sol/gel transition. Scanning electron microscopy (SEM) measurements reveal a microporous structure in form of flakes for the three of them. The low pH at which these hydrogels are formed (pH < 4) limits their direct use as drug-delivery systems, but still this system constitutes a novel method for easy and fast conversion of small drugs into potent hydrogelators. Future developments will help to fully develop the idea in order to create a new class of supramolecular drug-delivery systems.