Water Supercharges Metabolic Disease Screening
A new method could dramatically cut the time and complexity of diagnosing inherited metabolic diseases – using just a few dried drops of blood, urine, or serum. The technique involves extracting dried samples and mixing them with positively charged water before direct infusion electrospray ionization-mass spectrometry (ESI-MS) analysis.
The new approach enabled simultaneous detection of nine amino acids and seven acylcarnitines, covering most IMDs routinely screened in hospitals. Compared with standard liquid chromatography-tandem mass spectrometry (LC-MS/MS), the method delivered up to tenfold sensitivity improvements and faster turnaround. The enhanced sensitivity was linked to charged water’s capacity to reduce salt interference and concentrate charge around target analytes, offsetting the usual ionization suppression caused by its high surface tension
Validation against LC-MS/MS and successful application to clinical serum samples confirmed the method’s utility. The authors propose it as a simple, efficient alternative for routine IMD diagnostics – offering speed and sensitivity with minimal sample preparation.
How Extremophiles Fine-Tune their Molecular Machinery
Researchers have identified a previously unknown tRNA-modifying enzyme in the hyperthermophilic archaeon Thermococcus kodakarensis that may help it to survive near-boiling temperatures. The enzyme, TrmTS, installs a 2′-O-methylcytidine (Cm⁶) modification on tryptophan tRNA – an alteration thought to stabilize RNA structure under extreme heat.
To confirm the enzyme’s activity, the researchers used high-sensitivity RNA mass spectrometry, revealing that the recombinant TrmTS specifically catalyzes methylation of cytidine, adenosine, and uridine – but not guanosine – at the ribose 2′-hydroxyl group. When the trmTS gene was deleted, T. kodakarensis exhibited impaired growth at 93 °C, supporting the idea that Cm⁶ helps protect tRNA at high temperatures.
This discovery expands the known diversity of RNA-modifying enzymes and sheds light on how extremophiles fine-tune their molecular machinery to thrive in punishing environments.
Protein Aggregation Identified as Cause of RNA Splicing Defects
A new study from Mass General Brigham links protein aggregation to disrupted tRNA processing in GGC repeat expansion disorders, offering a mechanistic explanation for selective neurodegeneration in diseases like fragile X-associated tremor/ataxia syndrome (FXTAS) and neuronal intranuclear inclusion disease (NIID). The researchers demonstrated that polyglycine-containing protein aggregates sequester the tRNA ligase complex (tRNA-LC), impeding a key step in tRNA biogenesis.
Using proteomic profiling and mass spectrometry, the team identified that the aggregates recruit FAM98B – a glycine-rich subunit of the tRNA-LC – via its intrinsically disordered region. This interaction was confirmed in patient brain tissue, where FAM98B was depleted from the nucleoplasm and tRNA processing defects were observed. “Our work reveals a new and unexpected link between protein aggregation and RNA processing disorders in GGC repeat diseases,” said lead investigator Raghu Chivukula, in a recent Q&A.
Mouse models further supported the findings: depleting Fam98b in adult brains triggered motor deficits and gliosis. The results suggest that targeting tRNA splicing disruption could offer a therapeutic strategy across multiple repeat-associated neurodegenerative conditions.
Oat of Control
New research from Australian scientists has uncovered key molecular regulators of oil production in oats, paving the way for breeding low-oil varieties better suited for milling and plant-based food markets. Using proteomics, lipidomics, and mass spectrometry imaging, the study identified the enzymes and lipid accumulation patterns that distinguish high-oil and medium-oil oat cultivars during grain development.
Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) localized triacylglycerol (TG) accumulation to the endosperm, while LC-MS/MS and protein clustering revealed that lipid biosynthesis pathways – especially fatty acid synthesis (FAS) – become active from 8 days after pollination. The high-oil variety Bannister exhibited elevated expression of key enzymes such as ACCase2, GPAT, and LPAAT, in contrast to the medium-oil Bilby, which showed greater starch synthesis activity.
The study also found evidence of a metabolic trade-off between oil and carbohydrate synthesis, suggesting that carbon flux in Bannister is preferentially routed to lipid production. "This research provides important insights into the biological mechanisms underlying varietal differences of oil production in developing oat grains," commented Janine Croser in the team’s press release.
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