Direct conversion of carlactonoic acid to orobanchol by cytochrome P450 CYP722C in strigolactone biosynthesis

Strigolactones (SLs) are carotenoid-derived phytohormones and rhizosphere signaling molecules for arbuscular mycorrhizal fungi and root parasitic weeds. Why and how plants produce diverse SLs are unknown. Here, cytochrome P450 CYP722C is identified as a key enzyme that catalyzes the reaction of BC-ring closure leading to orobanchol, the most prevalent canonical SL. The direct conversion of carlactonoic acid to orobanchol without passing through 4-deoxyorobanchol is catalyzed by the recombinant enzyme. By knocking out the gene in tomato plants, orobanchol was undetectable in the root exudates, whereas the architecture of the knockout and wild-type plants was comparable. These findings add to our understanding of the function of the diverse SLs in plants and suggest the potential of these compounds to generate crops with greater resistance to infection by noxious root parasitic weeds

Parkinson’s disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling

Mutations in the iPLA2-VIA/PLA2G6 gene are responsible for PARK14-linked Parkinson’s disease (PD) with α-synucleinopathy. However, it is unclear how iPLA2-VIA mutations lead to α-synuclein (α-Syn) aggregation and dopaminergic (DA) neurodegeneration. Here, we report that iPLA2-VIA–deficient Drosophila exhibits defects in neurotransmission during early developmental stages and progressive cell loss throughout the brain, including degeneration of the DA neurons. Lipid analysis of brain tissues reveals that the acyl-chain length of phospholipids is shortened by iPLA2-VIA loss, which causes endoplasmic reticulum (ER) stress through membrane lipid disequilibrium. The introduction of wild-type human iPLA2-VIA or the mitochondria–ER contact site-resident protein C19orf12 in iPLA2-VIA–deficient flies rescues the phenotypes associated with altered lipid composition, ER stress, and DA neurodegeneration, whereas the introduction of a disease-associated missense mutant, iPLA2-VIA A80T, fails to suppress these phenotypes. The acceleration of α-Syn aggregation by iPLA2-VIA loss is suppressed by the administration of linoleic acid, correcting the brain lipid composition. Our findings suggest that membrane remodeling by iPLA2-VIA is required for the survival of DA neurons and α-Syn stability

Transabdominal Ultrasound Real-time Tissue Elastography as a Screening Method for Early Chronic Pancreatitis

Background and Purpose: The concept of early chronic pancreatitis was proposed in Japan with the aim to improve the prognosis of patients with chronic pancreatitis. Endoscopic ultrasonography plays an important role in early diagnoses, but is limited by its invasiveness and poor objectivity. Hence, this study aimed to determine the usefulness of transabdominal ultrasound real-time tissue elastography as a screening method for early chronic pancreatitis. Methods: We retrospectively examined 73 patients who underwent simultaneous ultrasound real-time tissue elastography and endoscopic ultrasonography from 2011 to 2014. The correlation between feature values (MEAN, %AREA, COMP) calculated by real-time tissue elastography and the Rosemont classification of endoscopic ultrasonography diagnostic criteria for chronic pancreatitis, and the diagnostic ability of ultrasound real-time tissue elastography to recognize “indeterminate for chronic pancreatitis” findings, which correspond to early chronic pancreatitis, were evaluated. Main Results: Based on the Rosemont classification, 26 patients were “normal”, 16 were “indeterminate for chronic pancreatitis”, 13 were “suggestive of chronic pancreatitis”, and 18 were “consistent with chronic ancreatitis”. There were significant correlations between the feature values (MEAN, %AREA, COMP) and the Rosemont classification (p < 0.001; ρ = –0.788, 0.779, and 0.489, respectively). The area under the curve for the ability of MEAN to diagnose “indeterminate for chronic pancreatitis” was 0.889 (sensitivity, 93.8%; specificity, 76.9%). Conclusions: The feature values calculated by ultrasound real-time tissue elastography were correlated with the Rosemont classification. Ultrasound real-time tissue elastography may be a useful screening method for early chronic pancreatitis

Srsf7 Establishes the Juvenile Transcriptome through Age-Dependent Alternative Splicing in Mice.

The juvenile phase is characterized by continuously progressing physiological processes such as growth and maturation, which are accompanied by transitions in gene expression. The contribution of transcriptome dynamics to the establishment of juvenile properties remains unclear. Here, we investigated alternative splicing (AS) events in postnatal growth and elucidated the landscape of age-dependent alternative splicing (ADAS) in C57BL/6 mice. Our analysis of ADAS in the cerebral cortex, cardiomyocytes, and hepatocytes revealed numerous juvenile-specific splicing isoforms that shape the juvenile transcriptome, which in turn functions as a basis for the highly anabolic status of juvenile cells. Mechanistically, the juvenile-expressed splicing factor Srsf7 mediates ADAS, as exemplified by switching from juvenile to adult forms of anabolism-associated genes Eif4a2 and Rbm7. Suppression of Srsf7 results in "fast-forwarding" of this transcriptome transition, causing impaired anabolism and growth in mice. Thus, juvenile-specific AS is indispensable for the anabolic state of juveniles and differentiates juveniles from adults

Neuroepithelial cell competition triggers loss of cellular juvenescence.

Cell competition is a cell-cell interaction mechanism which maintains tissue homeostasis through selective elimination of unfit cells. During early brain development, cells are eliminated through apoptosis. How cells are selected to undergo elimination remains unclear. Here we aimed to identify a role for cell competition in the elimination of suboptimal cells using an in vitro neuroepithelial model. Cell competition was observed when neural progenitor HypoE-N1 cells expressing RASV12 were surrounded by normal cells in the co-culture. The elimination through apoptosis was observed by cellular changes of RASV12 cells with rounding/fragmented morphology, by SYTOX blue-positivity, and by expression of apoptotic markers active caspase-3 and cleaved PARP. In this model, expression of juvenility-associated genes Srsf7 and Ezh2 were suppressed under cell-competitive conditions. Srsf7 depletion led to loss of cellular juvenescence characterized by suppression of Ezh2, cell growth impairment and enhancement of senescence-associated proteins. The cell bodies of eliminated cells were engulfed by the surrounding cells through phagocytosis. Our data indicates that neuroepithelial cell competition may have an important role for maintaining homeostasis in the neuroepithelium by eliminating suboptimal cells through loss of cellular juvenescence

Gm14230 controls Tbc1d24 cytoophidia and neuronal cellular juvenescence.

It is not fully understood how enzymes are regulated in the tiny reaction field of a cell. Several enzymatic proteins form cytoophidia, a cellular macrostructure to titrate enzymatic activities. Here, we show that the epileptic encephalopathy-associated protein Tbc1d24 forms cytoophidia in neuronal cells both in vitro and in vivo. The Tbc1d24 cytoophidia are distinct from previously reported cytoophidia consisting of inosine monophosphate dehydrogenase (Impdh) or cytidine-5\u27-triphosphate synthase (Ctps). Tbc1d24 cytoophidia is induced by loss of cellular juvenescence caused by depletion of Gm14230, a juvenility-associated lncRNA (JALNC) and zeocin treatment. Cytoophidia formation is associated with impaired enzymatic activity of Tbc1d24. Thus, our findings reveal the property of Tbc1d24 to form cytoophidia to maintain neuronal cellular juvenescence

Juvenility-associated lncRNA Gm14230 maintains cellular juvenescence.

Juvenile animals possess distinct properties that are missing in adults. These properties include capabilities for higher growth, faster wound healing, plasticity and regeneration. However, the molecular mechanisms underlying these juvenile physiological properties are not fully understood. To obtain insight into the distinctiveness of juveniles from adults at the molecular level, we assessed long noncoding RNAs (lncRNAs) that are highly expressed selectively in juvenile cells. The noncoding elements of the transcriptome were investigated in hepatocytes and cardiomyocytes isolated from juvenile and adult mice. Here, we identified 62 juvenility-associated lncRNAs (JAlncs), which are selectively expressed in both hepatocytes and cardiomyocytes from juvenile mice. Among these common (shared) JAlncs, Gm14230 is evolutionarily conserved and is essential for cellular juvenescence. Loss of Gm14230 impairs cell growth and causes cellular senescence. Gm14230 safeguards cellular juvenescence through recruiting the histone methyltransferase Ezh2 to Tgif2, thereby repressing the functional role of Tgif2 in cellular senescence. Thus, we identify Gm14230 as a juvenility-selective lncRNA required to maintain cellular juvenescence