Carotenoids are crucial for plant growth and human health. The finding of ORANGE (OR) protein as a pivotal regulator of carotenogenesis offers a unique opportunity to comprehensively understand the ...regulatory mechanisms of carotenoid accumulation and develop crops with enhanced nutritional quality. Here, we demonstrated that alteration of a single amino acid in a wild-type OR greatly enhanced its ability to promote carotenoid accumulation. Whereas overexpression ofORfrom Arabidopsis (Arabidopsis thaliana; AtOR) or from the agronomically important crop sorghum (Sorghum bicolor; SbOR) increased carotenoid levels up to 2-fold, expression ofAtORHis
(R90H) orSbORHis
(R104H) variants dramatically enhanced carotenoid accumulation by up to 7-fold in the Arabidopsis calli. Moreover, we found thatAtORAla
(R90A) functioned similarly toAtORHis
to promote carotenoid overproduction. Neither AtOR nor AtORHisgreatly affected carotenogenic gene expression. AtORHisexhibited similar interactions with phytoene synthase (PSY) as AtOR in posttranscriptionally regulating PSY protein abundance. AtORHistriggered biogenesis of membranous chromoplasts in the Arabidopsis calli, which shared structures similar to chromoplasts found in the curd of the orange cauliflower (Brassica oleracea) mutant. By contrast, AtOR did not cause plastid-type changes in comparison with the controls, but produced plastids containing larger and electron-dense plastoglobuli. The unique ability ofAtORHis
in mediating chromoplast biogenesis is responsible for its induced carotenoid overproduction. Our study demonstratesORHis/Ala
as powerful tools for carotenoid enrichment in plants, and provides insights into the mechanisms underlyingORHis
-regulated carotenoid accumulation.
Carotenoids have various roles in plant physiology. Plant carotenoids are synthesized in plastids and are highly abundant in the chromoplasts of ripening fleshy fruits. Considerable research efforts ...have been devoted to elucidating mechanisms that regulate carotenoid biosynthesis, yet, little is known about the mechanism that triggers storage capacity, mainly through chromoplast differentiation. The
Orange
gene (
OR
) product stabilizes phytoene synthase protein (PSY) and triggers chromoplast differentiation.
OR
underlies carotenoid accumulation in orange cauliflower and melon. The
OR
’s ‘golden SNP’, found in melon, alters the highly evolutionary conserved Arginine
108
to Histidine and controls β-carotene accumulation in melon fruit, in a mechanism yet to be elucidated. We have recently shown that similar carotenogenic metabolic flux is active in non-orange and orange melon fruit. This flux probably leads to carotenoid turnover but known carotenoid turnover products are not detected in non-orange fruit. Arrest of this metabolic flux, using chemical inhibitors or mutations, induces carotenoid accumulation and biogenesis of chromoplasts, regardless of the allelic state of
OR
. We suggest that the ‘golden SNP’ induces β-carotene accumulation probably by negatively affecting the capacity to synthesize downstream compounds. The accumulation of carotenoids induces chromoplast biogenesis through a metabolite-induced mechanism. Carotenogenic turnover flux can occur in non-photosynthetic tissues, which do not accumulate carotenoids. Arrest of this flux by the ‘golden SNP’ or other flux-arrest mutations is a potential tool for the biofortification of agricultural products with carotenoids.
Function gain to promote carotenoid overaccumulation affects chromoplast biogenesis.
Carotenoids are crucial for plant growth and human health. The finding of ORANGE (OR) protein as a pivotal ...regulator of carotenogenesis offers a unique opportunity to comprehensively understand the regulatory mechanisms of carotenoid accumulation and develop crops with enhanced nutritional quality. Here, we demonstrated that alteration of a single amino acid in a wild-type OR greatly enhanced its ability to promote carotenoid accumulation. Whereas overexpression of
OR
from Arabidopsis (
Arabidopsis thaliana
;
AtOR
) or from the agronomically important crop sorghum (
Sorghum bicolor
;
SbOR
) increased carotenoid levels up to 2-fold, expression of
AtOR
His
(R90H) or
SbOR
His
(R104H) variants dramatically enhanced carotenoid accumulation by up to 7-fold in the Arabidopsis calli. Moreover, we found that
AtOR
Ala
(R90A) functioned similarly to
AtOR
His
to promote carotenoid overproduction. Neither AtOR nor AtOR
His
greatly affected carotenogenic gene expression. AtOR
His
exhibited similar interactions with phytoene synthase (PSY) as AtOR in posttranscriptionally regulating PSY protein abundance. AtOR
His
triggered biogenesis of membranous chromoplasts in the Arabidopsis calli, which shared structures similar to chromoplasts found in the curd of the orange cauliflower (
Brassica oleracea
) mutant. By contrast, AtOR did not cause plastid-type changes in comparison with the controls, but produced plastids containing larger and electron-dense plastoglobuli. The unique ability of
AtOR
His
in mediating chromoplast biogenesis is responsible for its induced carotenoid overproduction. Our study demonstrates
OR
His/Ala
as powerful tools for carotenoid enrichment in plants, and provides insights into the mechanisms underlying
OR
His
-regulated carotenoid accumulation.
Objectives
Caring Contacts are an emerging intervention that aims to reduce distress and suicide risk after acute psychiatric care. This trial aimed to determine whether, during a pandemic, there was ...any evidence that the mental health benefits and reduction in suicidal ideation (SI) associated with delivering Caring Contacts to recently discharged psychiatric patients were greater than a control communication. The secondary objective was to identify whether the predicted benefits were greater among people living alone or those diagnosed with depression.
Method
A single-site pilot randomized clinical trial (n = 100), with patients recruited from the adult Inpatient Psychiatry Unit at Sunnybrook Health Sciences Centre, Toronto, Canada between August 2020 and May 2021. Participants were randomized (1:1) to the Caring Contact or control group. Participants received three Caring Contact or control communications via email or mail (on days 4, 21, and 56 post-discharge). Mental health symptoms were assessed using the self-report Hopkins Symptom Checklist-25 (HSCL-25) scores at discharge (baseline) and when participants received each communication. Analysis of variance was used for the primary comparisons and exploratory analyses for subgroups.
Results
Both groups experienced a significant worsening of mental health symptoms at all time points post-discharge relative to baseline. There were no significant differences between groups at any time point, however, on day 4 there was a 24.2% and 72.6% attenuated worsening in the Caring Contact group compared to the control group for total symptom severity and SI, respectively. There was no significant interaction effect for the depression subgroup or those living alone.
Conclusions
While this pilot study was not powered to identify significant differences between groups, results are indicative of feasibility and acceptability of the intervention and provide some indication that Caring Contacts may have benefited patients in the days following discharge, supporting the need for larger-scale trials. The study was registered with clinicaltrials.gov (study ID NCT04456062).
The flavonoids are phenylpropanoid-derived metabolites that are ubiquitous in plants, playing many roles in growth and development. Recently, we observed that fruit rinds of yellow casaba muskmelons ...(Cucumis melo‘Inodorous Group') accumulate naringenin chalcone, a yellow flavonoid pigment. With RNA-sequencing analysis of bulked segregants representing the tails of a population segregating for naringenin chalcone accumulation followed by fine mapping and genetic transformation, we identified a Kelch domain-containing F-box protein coding (CmKFB) gene that, when expressed, negatively regulates naringenin chalcone accumulation. Additional metabolite analysis indicated that downstream flavonoids are accumulated together with naringenin chalcone, whereas CmKFB expression diverts the biochemical flux toward coumarins and general phenylpropanoids. These results show thatCmKFBfunctions as a posttranscriptional regulator that diverts flavonoid metabolic flux.
•EMS mutagenesis of melon seeds resulted in a pro-lycopene accumulating fruit.•Fruit apocarotenoids composition was associated with carotenoids profile.•The mutant accumulated significantly higher ...amount of upstream carotenoids.•An A–T transversion in melon’s CRTISO resulted in two truncated forms of mRNAs.•Expression level of early carotenoid pathway genes was up-regulated in the mutant.
In order to broaden the available genetic variation of melon, we developed an ethyl methanesulfonate mutation library in an orange-flesh ‘Charentais’ type melon line that accumulates β-carotene. One mutagenized M2 family segregated for a novel recessive trait, a yellow–orange fruit flesh (‘yofI’). HPLC analysis revealed that ‘yofI’ accumulates pro-lycopene (tetra-cis-lycopene) as its major fruit pigment. The altered carotenoid composition of ‘yofI’ is associated with a significant change of the fruit aroma since cleavage of β-carotene yields different apocarotenoids than the cleavage of pro-lycopene. Normally, pro-lycopene is further isomerized by CRTISO (carotenoid isomerase) to yield all-trans-lycopene, which is further cyclized to β-carotene in melon fruit. Cloning and sequencing of ‘yofI’ CRTISO identified two mRNA sequences which lead to truncated forms of CRTISO. Sequencing of the genomic CRTISO identified an A–T transversion in ‘yofI’ which leads to a premature STOP codon. The early carotenoid pathway genes were up regulated in yofI fruit causing accumulation of other intermediates such as phytoene and ζ-carotene. Total carotenoid levels are only slightly increased in the mutant. Mutants accumulating pro-lycopene have been reported in both tomato and watermelon fruits, however, this is the first report of a non-lycopene accumulating fruit showing this phenomenon.
Deadenylases are best known for degrading the poly(A) tail during mRNA decay. The deadenylase family has expanded throughout evolution and, in mammals, consists of 12 Mg
-dependent 3'-end RNases with ...substrate specificity that is mostly unknown. Pontocerebellar hypoplasia type 7 (PCH7) is a unique recessive syndrome characterized by neurodegeneration and ambiguous genitalia. We studied 12 human families with PCH7, uncovering biallelic, loss-of-function mutations in TOE1, which encodes an unconventional deadenylase. toe1-morphant zebrafish displayed midbrain and hindbrain degeneration, modeling PCH-like structural defects in vivo. Surprisingly, we found that TOE1 associated with small nuclear RNAs (snRNAs) incompletely processed spliceosomal. These pre-snRNAs contained 3' genome-encoded tails often followed by post-transcriptionally added adenosines. Human cells with reduced levels of TOE1 accumulated 3'-end-extended pre-snRNAs, and the immunoisolated TOE1 complex was sufficient for 3'-end maturation of snRNAs. Our findings identify the cause of a neurodegenerative syndrome linked to snRNA maturation and uncover a key factor involved in the processing of snRNA 3' ends.
A 10-year-old male with prolonged fever, rash, and conjunctivitis presented to the emergency department with concern for Kawasaki disease, found to have myocarditis and PCR positive for SARS-CoV-2.
Recurrent gene dosage disorders impart substantial risk for psychopathology. Yet, understanding that risk is hampered by complex presentations that challenge classical diagnostic systems. Here, we ...present a suite of generalizable analytic approaches for parsing this clinical complexity, which we illustrate through application to XYY syndrome.
We gathered high-dimensional measures of psychopathology in 64 XYY individuals and 60 XY controls, plus additional interviewer-based diagnostic data in the XYY group. We provide the first comprehensive diagnostic description of psychiatric morbidity in XYY syndrome and show how diagnostic morbidity relates to functioning, subthreshold symptoms, and ascertainment bias. We then map behavioral vulnerabilities and resilience across 67 behavioral dimensions before borrowing techniques from network science to resolve the mesoscale architecture of these dimensions and links to observable functional outcomes.
Carriage of an extra Y-chromosome increases risk for diverse psychiatric diagnoses, with clinically impactful subthreshold symptomatology. Highest rates are seen for neurodevelopmental and affective disorders. A lower bound of < 25% of carriers are free of any diagnosis. Dimensional analysis of 67 scales details the profile of psychopathology in XYY, which survives control for ascertainment bias, specifies attentional and social domains as the most impacted, and refutes stigmatizing historical associations between XYY and violence. Network modeling compresses all measured symptom scales into 8 modules with dissociable links to cognitive ability, adaptive function, and caregiver strain. Hub modules offer efficient proxies for the full symptom network.
This study parses the complex behavioral phenotype of XYY syndrome by applying new and generalizable analytic approaches for analysis of deep-phenotypic psychiatric data in neurogenetic disorders.
Summary
The sugar content of Solanum lycopersicum (tomato) fruit is a primary determinant of taste and quality. Cultivated tomato fruit are characterized by near‐equimolar levels of the hexoses ...glucose and fructose, derived from the hydrolysis of translocated sucrose. As fructose is perceived as approximately twice as sweet as glucose, increasing its concentration at the expense of glucose can improve tomato fruit taste. Introgressions of the FgrH allele from the wild species Solanum habrochaites (LA1777) into cultivated tomato increased the fructose‐to‐glucose ratio of the ripe fruit by reducing glucose levels and concomitantly increasing fructose levels. In order to identify the function of the Fgr gene, we combined a fine‐mapping strategy with RNAseq differential expression analysis of near‐isogenic tomato lines. The results indicated that a SWEET protein was strongly upregulated in the lines with a high fructose‐to‐glucose ratio. Overexpressing the SWEET protein in transgenic tomato plants dramatically reduced the glucose levels and increased the fructose : glucose ratio in the developing fruit, thereby proving the function of the protein. The SWEET protein was localized to the plasma membrane and expression of the SlFgr gene in a yeast line lacking native hexose transporters complemented growth with glucose, but not with fructose. These results indicate that the SlFgr gene encodes a plasma membrane‐localized glucose efflux transporter of the SWEET family, the overexpression of which reduces glucose levels and may allow for increased fructose levels. This article identifies the function of the tomato Fgr gene as a SWEET transporter, the upregulation of which leads to a modified sugar accumulation pattern in the fleshy fruit. The results point to the potential of the inedible wild species to improve fruit sugar accumulation via sugar transport mechanisms.
Significance Statement
This paper identifies the function of the tomato Fgr gene as a SWEET transporter whose upregulation leads to a modified sugar accumulation pattern in the fleshy fruit. The results point to the potential of the inedible wild species to impact on fruit sugar accumulation via sugar transport mechanisms.
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