Biallelic variants in OGDH encoding oxoglutarate dehydrogenase lead to a neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities.

PURPOSE: This study aimed to establish the genetic cause of a novel autosomal recessive neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities. METHODS: We performed a detailed clinical characterization of 4 unrelated individuals from consanguineous families with a neurodevelopmental disorder. We used exome sequencing or targeted-exome sequencing, cosegregation, in silico protein modeling, and functional analyses of variants in HEK293 cells and Drosophila melanogaster, as well as in proband-derived fibroblast cells. RESULTS: In the 4 individuals, we identified 3 novel homozygous variants in oxoglutarate dehydrogenase (OGDH) (NM_002541.3), which encodes a subunit of the tricarboxylic acid cycle enzyme α-ketoglutarate dehydrogenase. In silico homology modeling predicts that c.566C>T:p.(Pro189Leu) and c.890C>A:p.(Ser297Tyr) variants interfere with the structure and function of OGDH. Fibroblasts from individual 1 showed that the p.(Ser297Tyr) variant led to a higher degradation rate of the OGDH protein. OGDH protein with p.(Pro189Leu) or p.(Ser297Tyr) variants in HEK293 cells showed significantly lower levels than the wild-type protein. Furthermore, we showed that expression of Drosophila Ogdh (dOgdh) carrying variants homologous to p.(Pro189Leu) or p.(Ser297Tyr), failed to rescue developmental lethality caused by loss of dOgdh. SpliceAI, a variant splice predictor, predicted that the c.935G>A:p.(Arg312Lys)/p.(Phe264_Arg312del) variant impacts splicing, which was confirmed through a mini-gene assay in HEK293 cells. CONCLUSION: We established that biallelic variants in OGDH cause a neurodevelopmental disorder with metabolic and movement abnormalities.

Evaluation of Polycaprolactone Electrospun Nanofiber-Composites for Artificial Skin Based on Dermal Fibroblast Culture.

The study's aim was to develop a dermal equivalent scaffold that can mimic the architecture and biological performance of the human dermis. Poly ε-caprolactone (PCL) electrospun nanofiber material (ENF) was assembled with polyethylene glycol diacrylate (PEGDA), sodium alginate (SA) and type I collagen (CG1) to develop three groups of dermal equivalent scaffolds. These scaffolds were named PEGDA-PCL, SA-PCL and CG1-PCL. Scanning electron microscopy (SEM) images of cell-free scaffolds' top and cross-sectional surface were collected and analyzed to examine internal morphology, specifically the adhesiveness of PCL fibers with the different scaffolds. Human dermal fibroblasts were cultured on each of the scaffolds. Cell viability studies including cell adhesion, cell differentiation and stress fiber production were conducted on each scaffold. Furthermore, the architectural integrity of each scaffold was verified by degradation analysis for 2 weeks by soaking each scaffold in phosphate-buffered saline (PBS) solution. Finally, we conducted rheological characteristics of each scaffold. Based on our results from the above analysis, the study concluded that CG1-PCL is best suitable for the dermal equivalent model and has potential to be used as a graft for skin repair.

Use of Polycaprolactone Electrospun Nanofiber Mesh in a Face Mask.

Electrospun nanofiber mesh has previously been used as an air filtration device. However, the qualification of polycaprolactone (PCL) nanofiber mesh cloth in face masks to protect individuals against airborne particles carrying microorganisms has yet to be investigated. The long-term goal of this study is to develop methods to use PCL nanofiber mesh to provide better protection against microorganisms. To achieve this goal, we observed the morphology, water droplet absorption, thermal (differential scanning calorimetry), mechanical, and airborne particle filtering capabilities, and also the microbial activities of a PCL cloth, to evaluate whether it is suitable to act as a filter in a face mask. We have produced a polycaprolactone (PCL) nanofiber cloth after electrospinning it onto a drum for 3 and 10 min, referred to hereafter as PCL-3 and PCL-10, respectively. Our study found that the middle protection layer (control) of the Henry Schein Earloop Procedure Mask contains pores (average diameter = 5.72 ± 0.62 µm) which are 48 times larger than the diameter of a microorganism an average diameter of ~120 nanometers. However, PCL-10 nanofiber membranes show pores with an average diameter of 1.42 ± 0.34 µm. Our contact angle measurement tests found that all the samples were very hydrophobic (contact angle values varied between 120 and 150 degrees). However, both PCL cloths' contact angle values were lower compared to the control. The produced PCL cloths showed a lower water droplet absorption compared to the control. Thermal studies found that PCL is stable in extreme conditions and no plasticizing effect occurs due to the presence of a solvent. Mechanical tests showed that PCL-10 cloth had higher strength and modulus compared to the control and PCL-3 under tension loading conditions. A vacuum experiment found that the PCL-10 fiber cloth could withstand a negative pressure of 18 Psi without any signs of breakage, and the mask was able to capture airborne particles and microorganisms. The feasibility of immobilizing anti-bacterial nanoparticles with PCL during electrospinning creates the future potential of producing an anti-bacterial face mask using PCL.