L-Ascorbate Biosynthesis Involves Carbon Skeleton Rearrangement in the Nematode Caenorhabditis elegans

Ascorbate (AsA) is required as a cofactor and is widely distributed in plants and animals. Recently, it has been suggested that the nematode Caenorhabditis elegans also synthesizes AsA. However, its biosynthetic pathway is still unknown. To further understand AsA biosynthesis in C. elegans, we analyzed the incorporation of the 13C atom into AsA using gas chromatography-mass spectrometry (GC-MS) in worms fed with D-Glc (1-13C)-labeled Escherichia coli. GC-MS analysis revealed that AsA biosynthesis in C. elegans, similarly to that in mammalian systems, involves carbon skeleton rearrangement. The addition of L-gulono-1,4-lactone, an AsA precursor in the mammalian pathway, significantly increased AsA level in C. elegans, whereas the addition of L-galactono-1,4-lactone, an AsA precursor in the plant and Euglena pathway, did not affect AsA level. The suppression of E03H4.3 (an ortholog of gluconolactonase) or the deficiency of F54D5.12 (an ortholog of L-gulono-1,4-lactone oxidase) significantly decreased AsA level in C. elegans. Although N2- and AsA-deficient F54D5.12 knockout mutant worm (tm6671) morphologies and the ratio of collagen to non-collagen protein did not show any significant differences, the mutant worms exhibited increased malondialdehyde levels and reduced lifespan compared with the N2 worms. In conclusion, our findings indicate that the AsA biosynthetic pathway is similar in C. elegans and mammals

The tertiary structure of the human Xkr8–Basigin complex that scrambles phospholipids at plasma membranes

Xkr8–Basigin is a plasma membrane phospholipid scramblase activated by kinases or caspases. We combined cryo-EM and X-ray crystallography to investigate its structure at an overall resolution of 3.8 Å. Its membrane-spanning region carrying 22 charged amino acids adopts a cuboid-like structure stabilized by salt bridges between hydrophilic residues in transmembrane helices. Phosphatidylcholine binding was observed in a hydrophobic cleft on the surface exposed to the outer leaflet of the plasma membrane. Six charged residues placed from top to bottom inside the molecule were essential for scrambling phospholipids in inward and outward directions, apparently providing a pathway for their translocation. A tryptophan residue was present between the head group of phosphatidylcholine and the extracellular end of the path. Its mutation to alanine made the Xkr8–Basigin complex constitutively active, indicating that it plays a vital role in regulating its scramblase activity. The structure of Xkr8–Basigin provides insights into the molecular mechanisms underlying phospholipid scrambling

Case report: Endoscopic endonasal transposterior clinoid approach for resection of posterior clinoid process meningioma: technical notes and literature review

BackgroundPosterior clinoid process (PCP) meningioma is an exceedingly rare entity. It remains the most challenging skull base lesion for neurosurgeons due to its treacherous location that insinuates amongst critical neurovascular structures. This article will describe the technical notes using the endoscopic endonasal approach that provide the earliest devascularization and detachment of the tumor PCP meningioma.MethodsWe are introducing the surgical implementation of an endoscopic endonasal approach to removing PCP meningioma. Furthermore, we perform a literature review of posterior clinoid process meningioma that undergoes surgical intervention, then summarize the benefits and limitations of each approach.ResultsWe present a case of right PCP meningioma that was removed using an endoscopic endonasal approach through the transposterior clinoid corridor in a 52-year-old-woman. We describe the technical notes in performing this approach to have the earliest devascularization and detachment of the tumor by performing posterior clinoidectomy. Safe tumor removal is performed with a wide and clear view of the surrounding neurovascular structure. Based on our database search, we found nine articles reported on the surgical management of PCP meningiomas, with a total number of 15 cases. All of the reported cases performed the tumor removal using the transcranial approach.ConclusionThe endoscopic endonasal transposterior clinoid approach circumvents all disadvantages faced by the traditional transcranial approach, providing the earliest approach to devascularized and detaching the tumor from its attachment at PCP. This approach demonstrates safety and efficacy, making it an acceptable alternative for PCP meningioma resections

The RRM domain of poly(A)-specific ribonuclease has a noncanonical binding site for mRNA cap analog recognition

The degradation of the poly(A) tail is crucial for posttranscriptional gene regulation and for quality control of mRNA. Poly(A)-specific ribonuclease (PARN) is one of the major mammalian 3′ specific exo-ribonucleases involved in the degradation of the mRNA poly(A) tail, and it is also involved in the regulation of translation in early embryonic development. The interaction between PARN and the m7GpppG cap of mRNA plays a key role in stimulating the rate of deadenylation. Here we report the solution structures of the cap-binding domain of mouse PARN with and without the m7GpppG cap analog. The structure of the cap-binding domain adopts the RNA recognition motif (RRM) with a characteristic α-helical extension at its C-terminus, which covers the β-sheet surface (hereafter referred to as PARN RRM). In the complex structure of PARN RRM with the cap analog, the base of the N7-methyl guanosine (m7G) of the cap analog stacks with the solvent-exposed aromatic side chain of the distinctive tryptophan residue 468, located at the C-terminal end of the second β-strand. These unique structural features in PARN RRM reveal a novel cap-binding mode, which is distinct from the nucleotide recognition mode of the canonical RRM domains

Torque-Sensing Soft Bellows Actuator for Multi-Fingered Hands Taking Bellow’s Buckling Into Consideration

Soft multi-fingered robotic hands are safe in human environments and can perform human-like behaviors. However, structural complexities and nonlinearities in soft actuators complicate torque sensing, a critical function for dexterous object manipulation. This study introduces a torque-sensing finger joint mechanism using a soft actuator composed of water-powered hydraulic bellows. Two real-time torque estimation methods are proposed, developed, and validated specifically for cases in which buckling occurs in the bellows, a situation that typically presents significant estimation challenges. The buckling spring model for torque estimation, explicitly considering the buckling effect, is a linear model that considers two elastic forces for the pressure and external force. The multi-layer perceptron model for torque estimation considers the nonlinearity of the actuator. The experimental results show that both methods can estimate the torque in real-time with high accuracy. The torque control for grasping fragile objects has also been examined in real-world scenarios. The findings indicate that, compared to the approach without torque control, successful and safe manipulation of the target objects is accomplished without causing detrimental deformation

Endoscopic Trans-Mini-Cylinder Biopsy for Intraparenchymal Brain Lesions

Objective: The biopsy procedure is intended to obtain an adequate specimen volume from the targeted area while ensuring minimal damage to the normal brain. We performed navigation-guided endoscopic biopsy using a small-diameter cylinder to reduce the invasiveness of the biopsy procedure and ensure a sufficient amount of tissue is collected. We examined whether it is possible to reduce brain tissue injury by using a small-diameter cylinder and improve safety and effectiveness by using an endoscope to directly observe the lesion and achieve hemostasis. Methods: Patients who underwent endoscopic biopsy surgery using a 6-mm-diameter cylinder for intraparenchymal lesions were enrolled in this study. Postoperative hematoma formation and the extent of trajectory scarring were assessed. Results: Fifty-two procedures performed on 51 patients were analyzed in this study. Postoperative neurological deterioration was not observed in any patient. A pathological diagnosis was made for all patients. Postoperative computed tomography revealed no hematoma after 49 procedures and a small hematoma after 3 procedures, and no patients required additional treatment. A postoperative trajectory scar less than 5 mm in diameter was observed after 30 procedures, a scar of 5–10 mm was observed after 19 procedures, a scar larger than 10 mm was observed after 3 procedures at 1 week after surgery, and 40, 6 and 0 scars were observed at 3 months after surgery. Conclusions: Endoscopic biopsy using a small-diameter cylinder is a possible alternative biopsy technique for intraparenchymal lesions. This surgical technique is useful, especially in patients at risk of hemorrhagic complications

L-Ascorbate Biosynthesis Involves Carbon Skeleton Rearrangement in the Nematode Caenorhabditis elegans

Ascorbate (AsA) is required as a cofactor and is widely distributed in plants and animals. Recently, it has been suggested that the nematode Caenorhabditis elegans also synthesizes AsA. However, its biosynthetic pathway is still unknown. To further understand AsA biosynthesis in C. elegans, we analyzed the incorporation of the 13C atom into AsA using gas chromatography-mass spectrometry (GC-MS) in worms fed with D-Glc (1-13C)-labeled Escherichia coli. GC-MS analysis revealed that AsA biosynthesis in C. elegans, similarly to that in mammalian systems, involves carbon skeleton rearrangement. The addition of L-gulono-1,4-lactone, an AsA precursor in the mammalian pathway, significantly increased AsA level in C. elegans, whereas the addition of L-galactono-1,4-lactone, an AsA precursor in the plant and Euglena pathway, did not affect AsA level. The suppression of E03H4.3 (an ortholog of gluconolactonase) or the deficiency of F54D5.12 (an ortholog of L-gulono-1,4-lactone oxidase) significantly decreased AsA level in C. elegans. Although N2- and AsA-deficient F54D5.12 knockout mutant worm (tm6671) morphologies and the ratio of collagen to non-collagen protein did not show any significant differences, the mutant worms exhibited increased malondialdehyde levels and reduced lifespan compared with the N2 worms. In conclusion, our findings indicate that the AsA biosynthetic pathway is similar in C. elegans and mammals