Verbascum species as a new source of saffron apocarotenoids and molecular tools for the biotechnological production of crocins and picrocrocin.

Crocins are glucosylated apocarotenoids present in flowers and fruits of a few plant species, including saffron, gardenia, and Buddleja. The biosynthesis of crocins in these plants has been unraveled, and the enzymes engineered for the production of crocins in heterologous systems. Mullein (Verbascum sp.) has been identified as a new source of crocins and picrocrocin. In this work, we have identified eight enzymes involved in the cleavage of carotenoids in two Verbascum species, V. giganteum and V. sinuatum. Four of them were homologous to the previously identified BdCCD4.1 and BdCCD4.3 from Buddleja, involved in the biosynthesis of crocins. These enzymes were analyzed for apocarotenogenic activity in bacteria and Nicotiana benthamiana plants using a virus-driven system. Metabolic analyses of bacterial extracts and N. benthamiana leaves showed the efficient activity of these enzymes to produce crocins using ß-carotene and zeaxanthin as substrates. Accumulations of 0.17% of crocins in N. benthamiana dry leaves were reached in only 2 weeks using a recombinant virus expressing VgCCD4.1, similar to the amounts previously produced using the canonical saffron CsCCD2L. The identification of these enzymes, which display a particularly broad substrate spectrum, opens new avenues for apocarotenoid biotechnological production.

Concurrent inhibition of ALK and SRC kinases disrupts the ALK lung tumor cell proteome.

Precision oncology has revolutionized the treatment of ALK-positive lung cancer with targeted therapies. However, an unmet clinical need still to address is the treatment of refractory tumors that contain drug-induced resistant mutations in the driver oncogene or exhibit resistance through the activation of diverse mechanisms. In this study, we established mouse tumor-derived cell models representing the two most prevalent EML4-ALK variants in human lung adenocarcinomas and characterized their proteomic profiles to gain insights into the underlying resistance mechanisms. We showed that Eml4-Alk variant 3 confers a worse response to ALK inhibitors, suggesting its role in promoting resistance to targeted therapy. In addition, proteomic analysis of brigatinib-treated cells revealed the upregulation of SRC kinase, a protein frequently activated in cancer. Co-targeting of ALK and SRC showed remarkable inhibitory effects in both ALK-driven murine and ALK-patient-derived lung tumor cells. This combination induced cell death through a multifaceted mechanism characterized by profound perturbation of the (phospho)proteomic landscape and a synergistic suppressive effect on the mTOR pathway. Our study demonstrates that the simultaneous inhibition of ALK and SRC can potentially overcome resistance mechanisms and enhance clinical outcomes in ALK-positive lung cancer patients. ONE SENTENCE SUMMARY: Co-targeting ALK and SRC enhances ALK inhibitor response in lung cancer by affecting the proteomic profile, offering hope for overcoming resistance and improving clinical outcomes.

Nanotube-Like Electronic States in [5,5]-C90 Fullertube Molecules.

Fullertubes, that is, fullerenes consisting of a carbon nanotube moiety capped by hemifullerene ends, are emerging carbon nanomaterials whose properties show both fullerene and carbon nanotube (CNT) traits. Albeit it may be expected that their electronic states show a certain resemblance to those of the extended nanotube, such a correlation has not yet been found or described. Here it shows a scanning tunneling microscopy (STM) and spectroscopy (STS) characterization of the adsorption, self-assembly, and electronic structure of 2D arrays of [5,5]-C90 fullertube molecules on two different noble metal surfaces, Ag(111) and Au(111). The results demonstrate that the shape of the molecular orbitals of the adsorbed fullertubes corresponds closely to those expected for isolated species on the grounds of density functional theory calculations. Moreover, a comparison between the electronic density profiles in the bands of the extended [5,5]-CNT and in the molecules reveals that some of the frontier orbitals of the fullertube molecules can be described as the result of the quantum confinement imposed by the hemifullerene caps to the delocalized band states in the extended CNT. The results thus provide a conceptual framework for the rational design of custom fullertube molecules and can potentially become a cornerstone in the understanding of these new carbon nanoforms.

Gene flow throughout the evolutionary history of a colour polymorphic and generalist clownfish.

Even seemingly homogeneous on the surface, the oceans display high environmental heterogeneity across space and time. Indeed, different soft barriers structure the marine environment, which offers an appealing opportunity to study various evolutionary processes such as population differentiation and speciation. Here, we focus on Amphiprion clarkii (Actinopterygii; Perciformes), the most widespread of clownfishes that exhibits the highest colour polymorphism. Clownfishes can only disperse during a short pelagic larval phase before their sedentary adult lifestyle, which might limit connectivity among populations, thus facilitating speciation events. Consequently, the taxonomic status of A. clarkii has been under debate. We used whole-genome resequencing data of 67 A. clarkii specimens spread across the Indian and Pacific Oceans to characterize the species' population structure, demographic history and colour polymorphism. We found that A. clarkii spread from the Indo-Pacific Ocean to the Pacific and Indian Oceans following a stepping-stone dispersal and that gene flow was pervasive throughout its demographic history. Interestingly, colour patterns differed noticeably among the Indonesian populations and the two populations at the extreme of the sampling distribution (i.e. Maldives and New Caledonia), which exhibited more comparable colour patterns despite their geographic and genetic distances. Our study emphasizes how whole-genome studies can uncover the intricate evolutionary past of wide-ranging species with diverse phenotypes, shedding light on the complex nature of the species concept paradigm.

Ultrashort Pulse Excited Tip-Enhanced Raman Spectroscopy in Molecules.

Vibrational fingerprints of molecules and low-dimension materials can be traced with subnanometer resolution by performing Tip-enhanced Raman spectroscopy (TERS) in a scanning tunneling microscope (STM). Strong atomic-scale localization of light in the plasmonic nanocavity of the STM enables high spatial resolution in STM-TERS; however, the temporal resolution is so far limited. Here, we demonstrate stable TERS measurements from subphthalocyanine (SubPc) molecules excited by ∼500 fs long laser pulses in a low-temperature (LT) ultrahigh-vacuum (UHV) STM. The intensity of the TERS signal excited with ultrashort pulses scales linearly with the increasing flux of the laser pulses and exponentially with the decreasing gap-size of the plasmonic nanocavity. Furthermore, we compare the characteristic features of TERS excited with ultrashort pulses and with a continuous-wave (CW) laser. Our work lays the foundation for future experiments of time-resolved femtosecond TERS for the investigation of molecular dynamics with utmost spatial, temporal, and energy resolutions simultaneously.

Selectively Addressing Plasmonic Modes and Excitonic States in a Nanocavity Hosting a Quantum Emitter.

Controlling the interaction between the excitonic states of a quantum emitter and the plasmonic modes of a nanocavity is key for the development of quantum information processing devices. In this Letter we demonstrate that the tunnel electroluminescence of electrically insulated C60 nanocrystals enclosed in the plasmonic nanocavity at the junction of a scanning tunneling microscope can be switched from a broad emission spectrum, revealing the plasmonic modes of the cavity, to a narrow band emission, displaying only the excitonic states of the C60 molecules by changing the bias voltage applied to the junction. Interestingly, excitonic emission dominates the spectra in the high-voltage region in which the simultaneously acquired inelastic rate is low, demonstrating that the excitons cannot be created by an inelastic tunnel process. These results point toward new possible mechanisms for tunnel electroluminescence of quantum emitters and offer new avenues to develop electrically tunable nanoscale light sources.

Timed Up and Go in People with Subjective Cognitive Decline Is Associated with Faster Cognitive Deterioration and Cortical Thickness.

INTRODUCTION: Early markers of neurodegeneration provide an opportunity to detect, monitor, and initiate interventions in individuals who have an increased risk of developing dementia. Here, we investigated whether the Timed Up and Go (TUG) test is associated with early brain neurodegeneration and whether the TUG test could be a marker of cognitive decline in people with subjective cognitive decline (SCD). METHODS: This is a longitudinal analysis of the Dementia Disease Initiation Study, a prospective, community-based, cohort study from Norway, designed to investigate early markers of cognitive impairment and dementia. Participants were classified as SCD and healthy controls (HC). The main studied variables were the TUG test and cognition as measured by the Mini-Mental State Examination and the Consortium to Establish a Registry for Alzheimer's Disease memory composite score. Additionally, we investigated the cross-sectional association of brain morphology with the TUG using 1.5T-MRI. RESULTS: The sample included 45 participants (SCD = 21, HC = 24) followed during a mean time of 1.50 ± 0.70 years. At baseline, the cognitive performance did not differ between the groups, but TUG was longer in SCD. Slower baseline TUG was associated with a faster cognitive decline in both groups and it was also associated with reduced cortical thickness especially in motor, executive, associative, and somatosensory cortical regions in people with SCD. DISCUSSION/CONCLUSION: TUG predicted cognitive change in individuals with SCD, and there was a negative association between TUG and cortical thickness. TUG is a promising cheap and noninvasive marker of early cognitive decline and may help initiate interventions in individuals who have an increased risk of dementia.

Suicidal behavior in Mexican adolescents: A test of a latent class model using two independent probability samples.

Suicidal behavior is a serious health issue that affects the adolescent population and that may be prevented through evidence-based approaches. There are many risk factors involved in suicidal behavior, but there are few studies encompassing the complex relationships between them. This study tested the similarity between two latent class models from two different epidemiological samples of middle-school students and evaluated if the multinomial regression model replicated the associations between the classes and the psychosocial variables. Data of 4013 adolescents from the Mexican states of Campeche and Querétaro were included in LCA to characterize suicide behavior and associated factors. The most likely latent class membership was used as the outcome in multinomial regression models. The model with data from Querétaro was consistent with the previous LC model from Campeche. The four latent classes were nearly identical for both populations and can be defined as follows: 1) "No Problems," included 73% of the adolescents; 2) "Drug Use Only," comprised 7% of the adolescents; 3) "Suicidal Behavior, No Depression," captured 8% of the adolescents (25% reported binge drinking in the past month, 50% self-inflicted injuries, and 43% low-lethality suicide attempt); 4) "Depression and Suicidal Behavior," comprised 12% of the sample (66% met criteria for Major Depressive Episode, 28% reported binge drinking in the past month, and 11% had a high-lethality suicide attempt). The congruence between the models and the consistency with identified factors highlight the need for appropriate and effective prevention strategies to minimize risk factors and reinforce protective factors in the adolescent population.

Understanding saffron biology using omics- and bioinformatics tools: stepping towards a better Crocus phenome.

Saffron is a unique plant in many aspects, and its cellular processes are regulated at multiple levels. The genetic makeup in the form of eight chromosome triplets (2n = 3x = 24) with a haploid genetic content (genome size) of 3.45 Gbp is decoded into different types of RNA by transcription. The RNA then translates into peptides and functional proteins, sometimes involving post-translational modifications too. The interactions of the genome, transcriptome, proteome and other regulatory molecules ultimately result in the complex set of primary and secondary metabolites of saffron metabolome. These complex interactions manifest in the form of a set of traits 'phenome' peculiar to saffron. The phenome responds to the environmental changes occurring in and around saffron and modify its response in respect of growth, development, disease response, stigma quality, apocarotenoid biosynthesis, and other processes. Understanding these complex relations between different yet interconnected biological activities is quite challenging in saffron where classical genetics has a very limited role owing to its sterility, and the absence of a whole-genome sequence. Omics-based technologies are immensely helpful in overcoming these limitations and developing a better understanding of saffron biology. In addition to creating a comprehensive picture of the molecular mechanisms involved in apocarotenoid synthesis, stigma biogenesis, corm activity, and flower development, omics-technologies will ultimately lead to the engineering of saffron plants with improved phenome.

Electronic Temperature and Two-Electron Processes in Overbias Plasmonic Emission from Tunnel Junctions.

The accurate determination of electronic temperatures in metallic nanostructures is essential for many technological applications, like plasmon-enhanced catalysis or lithographic nanofabrication procedures. In this Letter, we demonstrate that the electronic temperature can be accurately measured by the shape of the tunnel electroluminescence emission edge in tunnel plasmonic nanocavities, which follows a universal thermal distribution with the bias voltage as the chemical potential of the photon population. A significant deviation between electronic and lattice temperatures is found below 30 K for tunnel currents larger than 15 nA. This deviation is rationalized as the result of a two-electron process in which the second electron excites plasmon modes with an energy distribution that reflects the higher temperature following the first tunneling event. These results dispel a long-standing controversy on the nature of overbias emission in tunnel junctions and adds a new method for the determination of electronic temperatures and quasiparticle dynamics.

Thymoquinone-Loaded Chitosan Nanoparticles as Natural Preservative Agent in Cosmetic Products.

The current status of controversy regarding the use of certain preservatives in cosmetic products makes it necessary to seek new ecological alternatives that are free of adverse effects on users. In our study, the natural terpene thymoquinone was encapsulated in chitosan nanoparticles. The nanoparticles were characterized by DLS and TEM, showing a particle size of 20 nm. The chemical structure, thermal properties, and release profile of thymoquinone were evaluated and showed a successful stabilization and sustained release of terpenes. The antimicrobial properties of the nanoparticles were evaluated against typical microbial contaminants found in cosmetic products, showing high antimicrobial properties. Furthermore, natural moisturizing cream inoculated with the aforementioned microorganisms was formulated with thymoquinone-chitosan nanoparticles to evaluate the preservative efficiency, indicating its promising use as a preservative in cosmetics.

Subfunctionalization of D27 Isomerase Genes in Saffron.

Chromoplasts and chloroplasts contain carotenoid pigments as all-trans- and cis-isomers, which function as accessory light-harvesting pigments, antioxidant and photoprotective agents, and precursors of signaling molecules and plant hormones. The carotenoid pathway involves the participation of different carotenoid isomerases. Among them, D27 is a ß-carotene isomerase showing high specificity for the C9-C10 double bond catalyzing the interconversion of all-trans- into 9-cis-ß-carotene, the precursor of strigolactones. We have identified one D27 (CsD27-1) and two D27-like (CsD27-2 and CsD27-3) genes in saffron, with CsD27-1 and CsD27-3, clearly differing in their expression patterns; specifically, CsD27-1 was mainly expressed in the undeveloped stigma and roots, where it is induced by Rhizobium colonization. On the contrary, CsD27-2 and CsD27-3 were mainly expressed in leaves, with a preferential expression of CsD27-3 in this tissue. In vivo assays show that CsD27-1 catalyzes the isomerization of all-trans- to 9-cis-ß-carotene, and could be involved in the isomerization of zeaxanthin, while CsD27-3 catalyzes the isomerization of all-trans- to cis-ζ-carotene and all-trans- to cis-neurosporene. Our data show that CsD27-1 and CsD27-3 enzymes are both involved in carotenoid isomerization, with CsD27-1 being specific to chromoplast/amyloplast-containing tissue, and CsD27-3 more specific to chloroplast-containing tissues. Additionally, we show that CsD27-1 is co-expressed with CCD7 and CCD8 mycorrhized roots, whereas CsD27-3 is expressed at higher levels than CRTISO and Z-ISO and showed circadian regulation in leaves. Overall, our data extend the knowledge about carotenoid isomerization and their implications in several physiological and ecological processes.

Crocus transcription factors CstMYB1 and CstMYB1R2 modulate apocarotenoid metabolism by regulating carotenogenic genes.

KEY MESSAGE: Two MYB genes have been identified which regulate apocarotenoid metabolism in Crocus sativus. Apocarotenoids like crocin, picrocrocin and safranal are restricted to genus Crocus and are synthesized by oxidative cleavage of zeaxanthin followed by glycosylation reactions. In Crocus sativus, these apocarotenoids are synthesized in stigma part of the flower in developmentally regulated manner. Most of the genes of apocarotenoid pathway are known, however, the mechanism that regulates its tissue and stage specific biosynthesis remains elusive. MYB family was identified as the largest transcription factor family from Crocus transciptome which indicated its possible role in apocarotenoid regulation besides regulating other metabolic pathways. Towards this, we started with identification of 150 MYB genes from Crocus transcriptome databases. The phylogenetic analysis of Crocus MYB genes divided them into 27 clusters. Domain analysis resulted in identification of four groups of MYBs depending upon the number of R repeats present. Expression profiling indicated that 12 MYBs are upregulated in stigma out of which expression of four genes CstMYB1, CstMYB14, CstMYB16 and CstMYB1R2 correlated with crocin accumulation. Transient overexpression of two nuclear localized MYB genes (CstMYB1 and CstMYB1R2) in Crocus confirmed their role in regulating carotenoid metabolism. Yeast-one-hybrid confirmed that CstMYB1 binds to carotenoid cleavage dioxygenase 2 (CCD2) promoter while CstMYB1R2 binds to phytoene synthase (PSY) and CCD2 promoters. Overall, our study established that CstMYB1 and CstMYB1R2 regulate apocarotenoid biosynthesis by directly binding to promoters of pathway genes.

Identification and characterization of apocarotenoid modifiers and carotenogenic enzymes for biosynthesis of crocins in Buddleja davidii flowers.

Crocetin biosynthesis in Buddleja davidii flowers proceeds through a zeaxanthin cleavage pathway catalyzed by two carotenoid cleavage dioxygenases (BdCCD4.1 and BdCCD4.3), followed by oxidation and glucosylation reactions that lead to the production of crocins. We isolated and analyzed the expression of 12 genes from the carotenoid pathway in B. davidii flowers and identified four candidate genes involved in the biosynthesis of crocins (BdALDH, BdUGT74BC1, BdUGT74BC2, and BdUGT94AA3). In addition, we characterized the profile of crocins and their carotenoid precursors, following their accumulation during flower development. Overall, seven different crocins, crocetin, and picrocrocin were identified in this study. The accumulation of these apocarotenoids parallels tissue development, reaching the highest concentration when the flower is fully open. Notably, the pathway was regulated mainly at the transcript level, with expression patterns of a large group of carotenoid precursor and apocarotenoid genes (BdPSY2, BdPDS2, BdZDS, BdLCY2, BdBCH, BdALDH, and BdUGT Genes) mimicking the accumulation of crocins. Finally, we used comparative correlation network analysis to study how the synthesis of these valuable apocarotenoids diverges among B. davidii, Gardenia jasminoides, and Crocus sativus, highlighting distinctive differences which could be the basis of the differential accumulation of crocins in the three species.

Benzodiazepines and antidepressants: Effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia.

OBJECTIVES: We aim to study the effects of the prescription of benzodiazepines and antidepressants on cognitive and functional decline in older adults living with Alzheimer's disease (AD) and Lewy body dementia (LBD) over a 5-year follow-up. METHODS: This is a longitudinal analysis of a Norwegian cohort study entitled "The Dementia Study of Western Norway" (DemVest). We included 196 patients newly diagnosed with AD (n = 111) and LBD (n = 85), followed annually for 5 years. Three prescription groups were defined: only benzodiazepines (BZD), only antidepressants (ADep), and the combination of benzodiazepines and antidepressants (BZD-ADep). Linear mixed-effects models were conducted to analyze the effect of the defined groups on the outcomes. The outcomes were functional decline, measured by the Rapid Disability Rating Scale-2, and cognition measured with the Mini-Mental State Examination. RESULTS: Prescription of the combination of benzodiazepines and antidepressants in LBD was associated with faster functional decline. In AD, the prescription of BZD and BZD-ADep was associated with greater functional deterioration. ADep alone did not show positive or negative significant associations with the studied outcomes. CONCLUSIONS: BZD and especially the combination of BZD and ADep are associated with functional decline in AD and LBD and should be used cautiously.

Quality of life in early-onset Alzheimer's disease due to a PSEN1-E280A mutation.

PURPOSE: The present study aims to explore the association between the quality of life (QoL) score and the clinical and sociodemographic variables in patients with the PSEN1-E280A mutation. We also seek to evaluate the differences between the QoL reported by the patients (P-QoL) and the scores reported by the caregivers (C-QoL). METHODS: An analysis of 75 patients with the PSEN1-E280A mutation with mild cognitive impairment and dementia was performed. We used the Quality of Life in Alzheimer Disease (QoL-AD) survey to evaluate QoL as an outcome and evaluated its association with sociodemographic, lifestyle, clinical, and past medical history variables. RESULTS: The largest difference in the median of the QoL-AD score was in those who needed help to eat, those with moderate or severe dementia, those classified as frail or pre-frail, those with moderate social risk, and those with depression. Also, C-QoL was lower than the P-QoL, and the QoL-AD of individuals with severe dementia was lower than for milder forms of the disease. Not needing help to eat, not having a stressful situation in the past 3 months, and the years of education were positively correlated with QoL-AD in the linear model. CONCLUSION: As studies in similar populations with AD, factors with more impact on QoL are those related to loss of functionality and independence. These factors are also associated with variables related to the current literature with the burden of the disease for the caregivers.

Body mass index, performance on activities of daily living and cognition: analysis in two different populations.

BACKGROUND: With this study, we aim to determine the associations of the different categories of the body mass index (BMI) with activities of daily living (ADL) and cognitive performance in two different populations living in the community; Colombian and South Korean older adults. METHODS: We performed a cross-sectional analysis of two surveys separately; The Survey on Health, Well-Being, and Aging in Colombia (SABE) (n = 23,343) and the Korean Longitudinal Study of aging (KLoSA) (n = 4556). Participants older than 50 years were selected from rural and urban areas achieving a representative sample. Here we investigated the association between BMI categories with function using zero-inflated negative binomial regressions, and with cognition using logistic regression models. RESULTS: After adjustment, in Colombia, underweight was associated with an impaired score on the Mini-mental State Examination (MMSE) and worse performance in the instrumental activities of daily living (IADL). Also, being overweight was associated with a better score on the MMSE and the IADL. For both outcomes education level significantly influenced the predictions. In South Korea, there were no significant associations for cognition, IADL, or basic activities of daily living (BADL). CONCLUSIONS: In the Colombian population, underweight, was associated with reduced cognitive performance and daily functioning. Additionally, being overweight but not obese was associated with better cognition and daily functioning. In South Korea, there were no significant associations between BMI and cognition, IADL, or BADL.

A New Glycosyltransferase Enzyme from Family 91, UGT91P3, Is Responsible for the Final Glucosylation Step of Crocins in Saffron (Crocus sativus L.).

Crocetin is an apocarotenoid formed from the oxidative cleavage of zeaxanthin, by the carotenoid cleavage enzymes CCD2 (in Crocus species) and specific CCD4 enzymes in Buddleja davidii and Gardenia jasminoides. Crocetin accumulates in the stigma of saffron in the form of glucosides and crocins, which contain one to five glucose molecules. Crocetin glycosylation was hypothesized to involve at least two enzymes from superfamily 1 UDP-sugar dependent glycosyltransferases. One of them, UGT74AD1, produces crocins with one and two glucose molecules, which are substrates for a second UGT, which could belong to the UGT79, 91, or 94 families. An in silico search of Crocus transcriptomes revealed six candidate UGT genes from family 91. The transcript profiles of one of them, UGT91P3, matched the metabolite profile of crocin accumulation, and were co-expressed with UGT74AD1. In addition, both UGTs interact in a two-hybrid assay. Recombinant UGT91P3 produced mostly crocins with four and five glucose molecules in vitro, and in a combined transient expression assay with CCD2 and UGT74AD1 enzymes in Nicotiana benthamiana. These results suggest a role of UGT91P3 in the biosynthesis of highly glucosylated crocins in saffron, and that it represents the last missing gene in crocins biosynthesis.

Biogenic Silver Nanoparticles from Iris tuberosa as Potential Preservative in Cosmetic Products.

Biogenic-silver nanoparticles emerge as new nanosilver platforms that allow us to obtain silver nanoparticles via "green chemistry". In our study, biogenic-silver nanoparticles were obtained from Iris tuberosa leaf extract. Nanoparticles were characterized by a UV-vis spectroscopy, dynamical light scattering technique. The transmission electron microscope revealed spheric and irregular nanoparticles with 5 to 50 nm in diameter. Antimicrobial properties were evaluated against typical microbial contaminants found in cosmetic products, showing high antimicrobial properties. Furthermore, natural moisturizing cream was formulated with biogenic-silver nanoparticles to evaluate the preservative efficiency through a challenge test, indicating its promising use as preservative in cosmetics.

Understanding suicidal behavior and its prevention among youth and young adults in Mexico.

Suicide rates in Mexico have increased and have more than doubled in the state of Aguascalientes over the past 10 years. Few studies have been able to control for family, neighborhood, and occupational environment factors that may confound the association between psychosocial characteristics and suicidal behavior. We study suicidal behavior among adolescents and young adults in Mexico utilizing epidemiologic research strategies to overcome prior research deficiencies. In a case-control study with youth and adults 14-42 years of age, recent cases of severe suicidal behavior (n = 150) were individually matched with up to three controls who had never had a suicidal attempt by age and sex, as well as within familial, neighborhood, and occupational contexts (n = 353). Data were collected through standardized face-to-face interviews to measure suicidal behavior and several covariates, including family relations, psychological resources, hopelessness, depression, self-esteem, stress, impulsivity, anxiety, and substance use. All measures demonstrated good to excellent precision and accuracy. Compared with their matched controls, cases perceived life events as more stressful and had worse depression and familial relationships; poorer development of affective, religious, and social resources; higher levels of hopelessness and impulsive behavior; and lower self-esteem. Evidence from multivariate analysis suggests highly probable MDE combined with low self-esteem and the use of two or more drugs in the past month more clearly differentiate cases and controls and, therefore, may best predict suicidal attempt among adolescents and young adults in Aguascalientes, Mexico.