Citrus Physiological and Molecular Response to Boron Stresses

Since the essentiality of boron (B) to plant growth was reported nearly one century ago, the implication of B in physiological performance, productivity and quality of agricultural products, and the morphogenesis of apical meristem in plants has widely been studied. B stresses (B deficiency and toxicity), which lead to atrophy of canopy and deterioration of Citrus fruits, have long been discovered in citrus orchards. This paper reviews the research progress of B stresses on Citrus growth, photosynthesis, light use efficiency, nutrient absorption, organic acid metabolism, sugar metabolism and relocation, and antioxidant system. Moreover, the beneficial effects of B on plant stress tolerance and further research in this area were also discussed.

Towards risk stratification and prediction of disease severity and mortality in COVID-19: Next generation metabolomics for the measurement of host response to COVID-19 infection

This study investigated the association between COVID-19 infection and host metabolic signatures as prognostic markers for disease severity and mortality. We enrolled 82 patients with RT-PCR confirmed COVID-19 infection who were classified as mild, moderate, or severe/critical based upon their WHO clinical severity score and compared their results with 31 healthy volunteers. Data on demographics, comorbidities and clinical/laboratory characteristics were obtained from medical records. Peripheral blood samples were collected at the time of clinical evaluation or admission and tested by quantitative mass spectrometry to characterize metabolic profiles using selected metabolites. The findings in COVID-19 (+) patients reveal changes in the concentrations of glutamate, valeryl-carnitine, and the ratios of Kynurenine/Tryptophan (Kyn/Trp) to Citrulline/Ornithine (Cit/Orn). The observed changes may serve as predictors of disease severity with a (Kyn/Trp)/(Cit/Orn) Receiver Operator Curve (ROC) AUC = 0.95. Additional metabolite measures further characterized those likely to develop severe complications of their disease, suggesting that underlying immune signatures (Kyn/Trp), glutaminolysis (Glutamate), urea cycle abnormalities (Cit/Orn) and alterations in organic acid metabolism (C5) can be applied to identify individuals at the highest risk of morbidity and mortality from COVID-19 infection. We conclude that host metabolic factors, measured by plasma based biochemical signatures, could prove to be important determinants of Covid-19 severity with implications for prognosis, risk stratification and clinical management.

Dandy-Walker malformation in methylmalonic acidemia: a rare case report

Background Methylmalonic acidemia is an organic acid metabolism disorder that usually has nonspecific clinical manifestations. Case presentation A 3-month-old female infant was admitted to the hospital for developmental retardation. Her prenatal and birth history was unremarkable. After admission, she developed dyspnea and severe anemia and was subsequently transferred to the intensive care unit. Magnetic resonance imaging of her brain showed a Dandy-Walker malformation, and metabolic screening indicated methylmalonic acidemia. Thus, she was diagnosed with methylmalonic acidemia and Dandy-Walker malformation. The patient underwent treatment including acidosis correction, blood transfusion, antibiotics, mechanical ventilation and heat preservation. Unfortunately, her condition progressively worsened and she died of metabolic crisis. Conclusions Dandy-Walker malformation may be a clinical manifestation of methylmalonic acidemia. Additionally, the co-existence of methylmalonic acidemia and Dandy-Walker malformation may be an uncharacterized syndrome which needs to be studied further.

The versatility of plant organic acid metabolism in leaves is underpinned by mitochondrial malate–citrate exchange

Malate and citrate underpin the characteristic flexibility of central plant metabolism by linking mitochondrial respiratory metabolism with cytosolic biosynthetic pathways. However, the identity of mitochondrial carrier proteins that influence both processes has remained elusive. Here we show by a systems approach that DICARBOXYLATE CARRIER 2 (DIC2) facilitates mitochondrial malate–citrate exchange in vivo in Arabidopsis thaliana. DIC2 knockout (dic2-1) retards growth of vegetative tissues. In vitro and in organello analyses demonstrate that DIC2 preferentially imports malate against citrate export, which is consistent with altered malate and citrate utilization in response to prolonged darkness of dic2-1 plants or a sudden shift to darkness of dic2-1 leaves. Furthermore, isotopic glucose tracing reveals a reduced flux towards citrate in dic2-1, which results in a metabolic diversion towards amino acid synthesis. These observations reveal the physiological function of DIC2 in mediating the flow of malate and citrate between the mitochondrial matrix and other cell compartments.

Transcriptome and Resequencing Analyses Provide Insight into Differences in Organic Acid Accumulation in Two Pear Varieties

Fruit acidity is one of the main determinants of fruit flavor and a target trait in fruit breeding. However, the genomic mechanisms governing acidity variation among different pear varieties remain poorly understood. In this study, two pear varieties with contrasting organic acid levels, ‘Dangshansuli’ (low-acidity) and ‘Amute’ (high-acidity), were selected, and a combination of transcriptome and population genomics analyses were applied to characterize their patterns of gene expression and genetic variation. Based on RNA-seq data analysis, differentially expressed genes (DEGs) involved in organic acid metabolism and accumulation were identified. Weighted correlation network analysis (WGCNA) revealed that nine candidate TCA (tricarboxylic acid)-related DEGs and three acid transporter-related DEGs were located in three key modules. The regulatory networks of the above candidate genes were also predicted. By integrating pear resequencing data, two domestication-related genes were found to be upregulated in ‘Amute’, and this trend was further validated for other pear varieties with high levels of organic acid, suggesting distinct selective sweeps during pear dissemination and domestication. Collectively, this study provides insight into organic acid differences related to expression divergence and domestication in two pear varieties, pinpointing several candidate genes for the genetic manipulation of acidity in pears.

Current Perspectives on Neonatal Screening for Propionic Acidemia in Japan: An Unexpectedly High Incidence of Patients with Mild Disease Caused by a Common PCCB Variant

Propionic acidemia (PA) is a disorder of organic acid metabolism which typically presents with acute encephalopathy-like symptoms associated with metabolic acidosis and hyperammonemia during the neonatal period. The estimated incidence of symptomatic PA in Japan is 1/400,000. The introduction of neonatal screening using tandem mass spectrometry has revealed a far higher disease frequency of approximately 1/45,000 live births due to a prevalent variant of c.1304T>C (p.Y435C) in PCCB, which codes β-subunit of propionyl-CoA carboxylase. Our questionnaire-based follow-up study reveals that most of these patients remain asymptomatic. However, reports on symptomatic patients exhibiting cardiac complications such as cardiomyopathy and QT prolongation have been increasing. Moreover, there were even cases in which these cardiac complications were the only symptoms related to PA. A currently ongoing study is investigating the risk of cardiac complications in patients with neonatal screening-detected PA caused by this common variant.

Glutaric Acidemia type 1 with Atypical Acylcarnitine Profile During Newborn Screening

Background and aims Glutaric acidemia type 1 (GA1) is a treatable disorder of cerebral organic acid metabolism caused by a defective glutaryl-CoA dehydrogenase (GCDH) gene. There is scarcity of reports of GA1 diagnoses following newborn screening (NBS) in the Chinese population. We assessed the acylcarnitine profiles and genetic characteristics of patients with GA1 identified via NBS.Materials and methods From January 2014 to September 2020, a total of 517,484 newborns screened by tandem mass spectrometry were recruited for this study. Newborns with elevated isovalerylcarnitine (C5DC) levels were recalled, those who tested positive on second screen were referred for confirmatory tests.Results Of 517,484 screened newborns, thirteen patients were diagnosed with GA1, including eleven neonatal GA1 and two maternal GA1 patients. The incidence of GA1 in the Quanzhou region was estimated to be 1 in 47,044 newborns. The initial NBS results showed that all but one of the patients had moderately or markedly increased C5DC levels. The neonatal GA1 patient with low free carnitine (C0) level suggestive of primary carnitine deficiency (PCD) while just the contrary to a typical GA1. Nine neonatal GA1 patients underwent urinary organic acid analyses: eight had elevated GA levels and one was reported in the normal range. Ten distinct GCDH variants were identified, eight were previously reported and two were newly identified. In silico prediction tools and protein modelling analysis suggested that the newly identified variants were potentially pathogenic. The most common variant was c.1244-2A > C, which had an allelic frequency of 54.55% (12/22), followed by c.1261G > A (p.Ala421Thr) (9.09%, 2/22). Conclusions GA1 patients may show only with low C0 levels at the initial screening and recall stages that may be overlooked. Maternal GA1 patients can also be detected during NBS duo to the low C0 levels in their infants. Therefore, PCD should be included in the differential diagnosis for GA1, and multigene panel testing should be performed in newborns with low C0 levels.