Molecular insights into codon usage analysis of mitochondrial fission and fusion gene: relevance to neurodegenerative diseases.

Mitochondrial dysfunction is the leading cause of neurodegenerative disorders like Alzheimer's disease and Parkinson's disease. Mitochondria is a highly dynamic organelle continuously undergoing the process of fission and fusion for even distribution of components and maintaining proper shape, number, and bioenergetic functionality. A set of genes governs the process of fission and fusion. OPA1, Mfn1, and Mfn2 govern fusion, while Drp1, Fis1, MIEF1, and MIEF2 genes control fission. Determination of specific molecular patterns of transcripts of these genes revealed the impact of compositional constraints on selecting optimal codons. AGA and CCA codons were over-represented, and CCC, GTC, TTC, GGG, ACG were under-represented in the fusion gene set. In contrast, CTG was over-represented, and GCG, CCG, and TCG were under-represented in the fission gene set. Hydropathicity analysis revealed non-polar protein products of both fission and fusion gene set transcripts. AGA codon repeats are an integral part of translational regulation machinery and present a distinct pattern of over-representation and under-representation in different transcripts within the gene sets, suggestive of selective translational force precisely controlling the occurrence of the codon. Out of six synonymous codons, five synonymous codons encoding for leucine were used differently in both gene sets. Hence, forces regulating the occurrence of AGA and five synonymous leucine-encoding codons suggest translational selection. A correlation of mutational bias with gene expression and codon bias and GRAVY and AROMA signifies the selection pressure in both gene sets, while the correlation of compositional bias with gene expression, codon bias, protein properties, and minimum free energy signifies the presence of compositional constraints. More than 25% of codons of both gene sets showed a significant difference in codon usage. The overall analysis shed light on molecular features of gene sets involved in fission and fusion.

Synthetic biology approach revealed enhancement in haeme oxygenase-1 gene expression by codon pair optimization while reduction by codon deoptimization.

Haem oxygenase-1 (HO-1) is a ubiquitously expressed gene involved in cellular homoeostasis, and its imbalance in expression results in various disorders. To alleviate such disorders, HO-1 gene expression needs to be modulated. Codon usage bias results from evolutionary forces acting on any nucleotide sequence and determines the gene expression. Like codon usage bias, codon pair bias also exists, playing a role in gene expression. In the present study, HO-1 gene was recoded by manipulating codon and codon pair bias, and four such constructs were made through codon/codon pair deoptimization and codon/codon pair optimization to reduce and enhance the HO-1 gene expression. Codon usage analysis was done for these constructs for four tissues brain, heart, pancreas and liver. Based on codon usage in different tissues, gene expression of these tissues was determined in terms of the codon adaptation index. Based on the codon adaptation index, minimum free energy, and translation efficiency, constructs were evaluated for enhanced or decreased HO-1 expression. The analysis revealed that for enhancing gene expression, codon pair optimization, while for reducing gene expression, codon deoptimization is efficacious. The recoded constructs developed in the study could be used in gene therapy regimens to cure HO-1 over or underexpression-associated disorders.

Implications of endoplasmic reticulum stress and beta-cell loss in immunodeficient diabetic NRG-Akita mice for understanding monogenic diabetes.

BACKGROUND: Immunodeficient mice models have become increasingly important as in vivo models engrafted with human cells or tissues for research. The NOD-Rag1null Ins2Akita Il2rnull (NRG Akita) mice is a model combined with immunodeficient NRG and monogenic diabetes Akita mice that develop spontaneous hyperglycemia with progressive loss of pancreatic insulin-producing beta-cells with age. This model is one of the monogenic diabetic models, which has been providing a powerful platform for transplantation experiments of stem cells-generated human ß-cells. This research aimed to provide insights into the mechanisms underlying this monogenic diabetes, which remains incompletely understood. METHODS: Histological and immunofluorescence analyses were conducted on endocrine pancreatic islets to compare NRG wild-type (Wt) controls with NRG-Akita mice. Our investigation focused on assessing the expression of endocrine hormones, transcription factors, proliferation, ER stress, and apoptosis. RESULTS: Histological analyses on NRG-Akita mice revealed smaller islets at 6-weeks-old, due to fewer ß-cells in the islets, compared to NRG-Wt controls, which further progressed with age. The proliferation rate decreased, and apoptosis was abundant in ß-cells in NRG Akita mice. Interestingly, our mechanistic analyses revealed that ß-cells in NRG-Akita mice progressively accumulated the endoplasmic reticulum (ER) stresses, leading to a decreased expression of pivotal ß-cell transcriptional factor PDX1. CONCLUSIONS: Altogether, our mechanistic insight into ß-cell loss in this model could shed light on essential links between ER stress, proliferation, and cell identity, which might open the door to new therapeutic strategies for various diseases since ER stress is one of the most common features not only in diabetes but also in other degenerative diseases.

Advancements and mechanisms of stem cell-based therapies for spinal cord injury in animals.

Spinal cord injury (SCI) is a neurodegenerative disorder of the central nervous system (CNS) that can lead to permanent loss of sensation and voluntary movement beyond the affected area. Extensive preclinical and clinical trials have been conducted to evaluate the safety and effectiveness of stem cells for the treatment of various CNS diseases or disorders, including SCI. However, several challenges hinder nerve cell regeneration in the injured spinal cord, such as extensive cell loss, limited neural cell regeneration capacity, axonal disruption, and the presence of growth-inhibiting molecules, particularly astroglial scarring or glial scars at the injury site in chronic cases. These obstacles pose significant challenges for physicians in restoring normal motor and sensory nerve function in both humans and animals following SCI. This review focuses on SCI pathogenesis, the mechanisms underlying the therapeutic potential of Mesenchymal Stem Cells (MSCs) in SCI, and the potential of stem cell-based therapies as promising avenues for treatment. This review article also included relevant preclinical and clinical data from animal studies.

Osteometric and topographic measurement of the skull and mandible of Siirt colored Mohair goat with three-dimensional (3D) modeling technique.

Siirt-colored Mohair goat is one of the breeds that contributed significantly to the existence of Mohair goats reared in Turkey. Morphological and morphometric characteristics of the Siirt-colored Mohair goat remained vague owing to a lack of studies. Recent advances in high-tech imaging have replaced conventional two-dimensional anatomical structures with three-dimensional (3D) models. In our study, morphometric features were determined by 3D modeling from computed tomography images obtained from the skull and mandibular bones of Siirt-colored Mohair goats. For this purpose, the skulls and mandibular bones of 20 Siirt-colored Mohair goats (10 females and 10 males) were used. The images were reconstructed with the help of a particular software program. The craniometric data were analyzed in terms of sexual dimorphism, and statistically significant difference was found in the A5, A18, and A31 measurement parameters (P<0.05) and Skull index (P<0.01) parameters. In the mandible measurements, there was a statistically significant difference between the sexes in C5, C10 measurement points (P<0.05), C2, C8, C12, C18, C21 measurement points (P<0.001) and surface area parameter (P<0.01). The morphometric data obtained is a resource in the fields of zoo archaeology, anatomy, forensics, anesthesia, surgery, and treatment.

Nanovaccines: A game changing approach in the fight against infectious diseases.

The field of nanotechnology has revolutionised global attempts to prevent, treat, and eradicate infectious diseases in the foreseen future. Nanovaccines have proven to be a valuable pawn in this novel technology. Nanovaccines are made up of nanoparticles that are associated with or prepared with components that can stimulate the host's immune system. In addition to their delivery capabilities, the nanocarriers have been demonstrated to possess intrinsic adjuvant properties, working as immune cell stimulators. Thus, nanovaccines have the potential to promote rapid as well as long-lasting humoral and cellular immunity. The nanovaccines have several possible benefits, including site-specific antigen delivery, increased antigen bioavailability, and a diminished adverse effect profile. To avail these benefits, several nanoparticle-based vaccines are being developed, including virus-like particles, liposomes, polymeric nanoparticles, nanogels, lipid nanoparticles, emulsion vaccines, exomes, and inorganic nanoparticles. Inspired by their distinctive properties, researchers are working on the development of nanovaccines for a variety of applications, such as cancer immunotherapy and infectious diseases. Although a few challenges still need to be overcome, such as modulation of the nanoparticle pharmacokinetics to avoid rapid elimination from the bloodstream by the reticuloendothelial system, The future prospects of this technology are also assuring, with multiple options such as personalised vaccines, needle-free formulations, and combination nanovaccines with several promising candidates.

ChatGPT for Veterinary Anatomy Education: An Overview of the Prospects and Drawbacks / ChatGPT para la Educación en Anatomía Veterinaria: Una Descripción General de las Perspectivas y los Inconvenientes

SUMMARY: The integration of artificial intelligence in veterinary medical education has the potential to revolutionize the way students learn veterinary anatomy. ChatGPT, launched by OpenAI in November 2022, has been the fastest-growing artificial intelligence (AI) application as a learning tool in the past few months. ChatGPT is a virtual assistant that provides students with detailed and relevant anatomical knowledge based on internet sources. Apart from the advantages of ChatGPT in veterinary anatomy education, the challenges and limitations must also be considered, as highlighted in this letter. Further research and evaluation are necessary to ensure the optimal integration of the ChatGPT tool into veterinary anatomy education. ChatGPT can provide students with valuable insights and educational support but cannot replace hands-on experiences; dissection-based laboratory sessions remain essential for developing practical skills and spatial understanding in veterinary anatomy education.

La integración de la inteligencia artificial en la educación médica veterinaria tiene el potencial de revolucionar la forma en que los estudiantes aprenden anatomía veterinaria. ChatGPT, lanzado por OpenAI en noviembre de 2022, ha sido la aplicación de inteligencia artificial (IA) de más rápido crecimiento como herramienta de aprendizaje en los últimos meses. ChatGPT es un asistente virtual que brinda a los estudiantes conocimientos anatómicos detallados y relevantes basados en fuentes de Internet. Además de las ventajas de ChatGPT en la educación en anatomía veterinaria, también se deben considerar los desafíos y las limitaciones, como se destaca en esta carta. Se necesitan más investigaciones y evaluaciones para garantizar la integración óptima de la herramienta ChatGPT en la educación en anatomía veterinaria. ChatGPT puede proporcionar a los estudiantes información valiosa y apoyo educativo, pero no puede reemplazar las experiencias prácticas. Las sesiones de laboratorio basadas en disecciones siguen siendo esenciales para desarrollar habilidades prácticas y comprensión espacial en la educación de la anatomía veterinaria.