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Genetics
Published in Cathy Laver-Bradbury, Margaret J.J. Thompson, Christopher Gale, Christine M. Hooper, Child and Adolescent Mental Health, 2021
The human nuclear genome is arranged as 23 separate pairs of chromosomes, one set inherited from each parent. Only about 1% of the nuclear genome is protein coding, and this is known as the ‘exome’. The remainder of the genome consists of other DNA elements such as regulatory regions that control gene expression. In order to produce a protein, DNA within the cell nucleus is transcribed into messenger ribonucleic acid (mRNA), which is then transported out of the nucleus for protein synthesis (translation) in the ribosome. The sequences of bases, known as nucleotides, in the DNA and mRNA molecules determine the resulting protein. (See Figure 12.1).
Finding a Target
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
The diversity of proteins required for a cell to function are all transcribed from the cells instruction manual: deoxyribonucleic acid (DNA). The DNA resides within the cell nucleus, which is effectively the control centre for the cell. The nucleus is a membrane-bound structure containing pores to permit the selective passage of certain molecules required for cellular activity at this organelle. Nucleotides and polynucleotides, such as ribonucleic acid (RNA), continually diffuse in and out of the nucleus. The code for building the proteins of the cell are carried from the control centre on RNA to the cytoplasm where the information contained on these molecules is interpreted and translated into an amino acid sequence to assemble a protein to be used in the cell. Protein synthesis, along with most other cellular activities, is controlled from the genes contained within DNA.
Biological Clockworks
Published in Sue Binkley, Biological Clocks, 2020
A chronon model for the circadian clock makes use of the sequence of events by which proteins are synthesized in cells. A sequence of chemical bases in the genetic material in chromosomes of the nucleus (DNA) specified a sequence of complementary bases in the formation of a large molecule (RNA), a process called transcription. In turn, the RNA leaves the cell nucleus and provides instructions for forming the sequence of amino acids in proteins at the cellular organelles called ribosomes, a process called translation. A cell contains chronons, strands of DNA 200–2000 cistrons long, which are the rate-limiting components of transcription, and therefore provide the timing mechanism. In this model, transcription takes a certain duration of time at the end of which some substance synthesized at the ribosomes then diffuses back to the DNA to restart the cycle. The role of diffusion in this model provides an explanation for temperature compensation, because diffusion has a Q10 near 1.
Discovery of benzochromene derivatives first example with dual cytotoxic activity against the resistant cancer cell MCF-7/ADR and inhibitory effect of the P-glycoprotein expression levels
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Laila M. Al-Harbi, Eman A. Al-Harbi, Rawda M. Okasha, R. A. El-Eisawy, Mohammed A. A. El-Nassag, Hany M. Mohamed, Ahmed M. Fouda, Ahmed A. Elhenawy, Ahmed Mora, Ahmed M. El-Agrody, Heba K. A. El-Mawgoud
Cell cycle arrest and distribution were done using Propidium Iodide Flow Cytometry Kit (ab139418, Abcam, Cambridge, UK) as previously described79. Briefly, MCF-7/ADR cancer cells at 1 × 104 cells were cultured in 60-mm dishes in the presence of various tested compounds with a concentration equal to the IC50 value for 24 h. Cells were collected and washed with PBS, fixed with precooled 70% ethanol at 4 °C. Staining went along in PBS containing 40 μg/ml RNase A and 10 μg/mL propidium iodide (PI) in the dark for 15 min. The DNA content in each cell nucleus was determined by a FACS Calibur flow cytometer (BD Biosciences, Franklin Lakes, NJ). Finally, Cell cycle phase distribution was analysed using Cell Quest Pro software (BD Biosciences) showing collected PI fluorescence intensity on FL2.
Exploiting active nuclear import for efficient delivery of Auger electron emitters into the cell nucleus
Published in International Journal of Radiation Biology, 2023
Andrey A. Rosenkranz, Tatiana A. Slastnikova, Mikhail O. Durymanov, Georgii P. Georgiev, Alexander S. Sobolev
For most of the cellular life, the contents of the cell nucleus are separated from the cytoplasm by the nuclear envelope, which consists of two phospholipidic membranes and intermembrane space that are permeated by numerous NPC (Lin and Hoelz 2019). NPCs are supramolecular protein structures that form rounded holes in the nuclear envelope where both nuclear membranes are fused. NPCs are embedded within these holes and form a stable protein scaffold. On the nuclear side, the scaffold forms eight extended fibers that are connected in a distal ring and form the nuclear basket. Another eight flexible fibers extend into the cytoplasm. Additional fiber-like extensions in a central opening generate the permeability barrier, which controls the import and export of macromolecules (Knockenhauer and Schwartz 2016). The main components of the eukaryotic NPC, called nucleoporins, are a family of approximately 30 proteins that form a part of the scaffolding and transport functions of NPC. The outer diameter, inner diameter of the central transport channel, height, and molecular mass of the human NPC is approximately 120 nm, 42.5 nm, 80 nm, and 110 MDa, respectively (Lin and Hoelz 2019).
Distribution of Aquaporin-4 channels in hippocampus and prefrontal cortex in mk-801-treated balb/c mice
Published in Ultrastructural Pathology, 2022
Omer Burak Ericek, Kübra Akillioglu, Dilek Saker, Ibrahim Cevik, Meltem Donmez Kutlu, Samet Kara, Dervis Mansuri Yilmaz
The nerve cell bodies in the gray matter, myelin-free nerve fibers, and glial cells, as well as the myelinated axons in the white matter, and the fine structures of the glial cells, were evaluated in the electron microscopic examination of the tissue samples of prefrontal cortex in the control group treated with normal saline. The nerve cell perikaryon in the gray matter was found to consist of a centrally located nucleus and a perinuclear cytoplasm surrounding it. The spherical cell nucleus was in the center of the cell. There was a well-distinguishable nucleolus in the vesicular-type nucleus. The mitochondria in the neuron cytoplasm were either ovoid or round-shaped and had both transverse and longitudinal-type cristae. The Golgi complex with the perinuclear settlement was observed in large numbers scattered throughout the perikaryon Neuroglial cells settled in the prefrontal cortex were generally found to have a spherical or ovoid nucleus and a perinuclear thin cytoplasmic ring surrounding the nucleus. In myelinated nerve fibers, it was observed that the myelin sheath had a regular lamellar structure. In axon cytoplasms, mitochondria, several neurotubules, and neurofilaments were remarkable (Figure 10(a-c)).