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Topic Review
LAG3
Lymphocyte-activation gene 3, also known as LAG-3, is a protein which in humans is encoded by the LAG3 gene. LAG3, which was discovered in 1990 and was designated CD223 (cluster of differentiation 223) after the Seventh Human Leucocyte Differentiation Antigen Workshop in 2000, is a cell surface molecule with diverse biologic effects on T cell function. It is an immune checkpoint receptor and as such is the target of various drug development programs by pharmaceutical companies seeking to develop new treatments for cancer and autoimmune disorders. In soluble form it is also being developed as a cancer drug in its own right.
  • 661
  • 02 Nov 2022
Topic Review
Glucose 6-P Dehydrogenase in Skeletal Muscle during Exercise
Hypomorphic Glucose 6-P dehydrogenase (G6PD) catalyzes the rate-limiting step in the pentose phosphate pathway (PPP), which provides the precursors of nucleotide synthesis for DNA replication as well as reduced nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is involved in the detoxification of cellular reactive oxygen species (ROS) and de novo lipid synthesis. An association between increased PPP activity and the stimulation of cell growth has been reported in different tissues including the skeletal muscle, liver, and kidney. PPP activity is increased in skeletal muscle during embryogenesis, denervation, ischemia, mechanical overload, the injection of myonecrotic agents, and physical exercise. In fact, the highest relative increase in the activity of skeletal muscle enzymes after one bout of exhaustive exercise is that of G6PD, suggesting that the activation of the PPP occurs in skeletal muscle to provide substrates for muscle repair. The age-associated loss in muscle mass and strength leads to a decrease in G6PD activity and protein content in skeletal muscle. G6PD overexpression in Drosophila Melanogaster and mice protects against metabolic stress, oxidative damage, and age-associated functional decline, and results in an extended median lifespan. 
  • 979
  • 02 Nov 2022
Topic Review
Copy-number Variation
Copy number variation (CNV) is a phenomenon in which sections of the genome are repeated and the number of repeats in the genome varies between individuals. Copy number variation is a type of structural variation: specifically, it is a type of duplication or deletion event that affects a considerable number of base pairs. Approximately two-thirds of the entire human genome may be composed of repeats and 4.8–9.5% of the human genome can be classified as copy number variations. In mammals, copy number variations play an important role in generating necessary variation in the population as well as disease phenotype. Copy number variations can be generally categorized into two main groups: short repeats and long repeats. However, there are no clear boundaries between the two groups and the classification depends on the nature of the loci of interest. Short repeats include mainly bi-nucleotide repeats (two repeating nucleotides e.g. A-C-A-C-A-C...) and tri-nucleotide repeats. Long repeats include repeats of entire genes. This classification based on size of the repeat is the most obvious type of classification as size is an important factor in examining the types of mechanisms that most likely gave rise to the repeats, hence the likely effects of these repeats on phenotype.
  • 806
  • 02 Nov 2022
Topic Review
Stress Accelerates Tumor Progression via Sympathetic Nervous System
The sympathetic nervous system (SNS) originates in the ventral brainstem, where sympathetic premotor neurons are found. They are found predominantly in the rostral ventrolateral medulla (RVLM) and in the rostral ventromedial medulla (RVMM). These neurons project to the intermediolateral nucleus (IML, also known as the sympathetic preganglionic nucleus), which then projects to the dorsal root ganglia (DRG) for terminal output to peripheral organs which control heart rate, blood pressure, respiration, glycemia, vigilance and other physiological responses. When negative emotions are induced under chronic stress, the sympathetic nervous system is continuously activated and increases the release of catecholamines (such as epinephrine and norepinephrine). In a spontaneous colon tumor model, ablation of sympathetic premotor neurons in APCmin/+ mice reduces the number of polyps in the mouse intestine. Sympathetic denervation also leads to decreased tumorigenesis in a spontaneous prostate tumor mouse model. These results suggest that loss of SNS function may slow tumorigenesis.
  • 466
  • 01 Nov 2022
Topic Review
Epoetin Alfa
Epoetin alfa is a human erythropoietin produced in cell culture using recombinant DNA technology. Authorised by the European Medicines Agency on 28 August 2007, it stimulates erythropoiesis (increasing red blood cell levels) and is used to treat anemia, commonly associated with chronic kidney failure and cancer chemotherapy. Epoetin is manufactured and marketed by Amgen under the brand name Epogen. Johnson & Johnson subsidiary Janssen Biotech (formerly Ortho Biotech Products, LP), sells the same drug under the name Procrit, pursuant to a product license agreement. The average cost per patient in the U.S. was $8,447 in 2009. Darbepoetin alfa (rINN) /dɑːrbəˈpɔɪtɪn/ is a glycosylation analog of erythropoietin containing two additional N-linked carbohydrate chains, also manufactured and marketed by Amgen, with a brand name of Aranesp. The Food and Drug Administration (FDA) warnings and safety precautions for Procrit, Epogen and Aranesp are identical. For several years, epoetin alfa has accounted for the single greatest drug expenditure paid by the U.S. Medicare system; in 2010, the program paid $2 billion for the drug. Raising hemoglobin levels has been found in some studies to be associated with higher risks of thrombotic events, strokes and death. It is on the World Health Organization's List of Essential Medicines.
  • 254
  • 01 Nov 2022
Topic Review
Bacteria-Based Cancer Treatment
Cancer refers to a disease involving abnormal cells that proliferate uncontrollably and can invade normal body tissue. It was estimated that at least 9 million patients are killed by cancer annually. Recent studies have demonstrated that bacteria play a significant role in cancer treatment and prevention. Owing to its unique mechanism of abundant pathogen-associated molecular patterns in antitumor immune responses and preferentially accumulating and proliferating within tumors, bacteria-based cancer immunotherapy has recently attracted wide attention.
  • 526
  • 31 Oct 2022
Topic Review
Alpha-Thalassemia
Alpha-thalassemia (α-thalassemia, α-thalassaemia) is a form of thalassemia involving the genes HBA1 and HBA2. Thalassemias are a group of inherited blood conditions which result in the impaired production of hemoglobin, the molecule that carries oxygen in the blood. Normal hemoglobin consists of two alpha chains and two beta chains; in alpha-thalassemia, there is a quantitative decrease in the amount of alpha chains, resulting in fewer normal hemoglobin molecules. Furthermore, alpha-thalassemia leads to the production of unstable beta globin molecules which cause increased red blood cell destruction. The degree of impairment is based on which clinical phenotype is present (how many genes are affected).
  • 537
  • 31 Oct 2022
Topic Review
WRKY Transcription Factor
The WRKY transcription factor family (pronounced ‘worky’) is a class of DNA-binding proteins. WRKY transcription factors are primarily specific to plants and algae (Viridiplantae); although, individual WRKY proteins do appear in the human protozoan parasite Giardia lamblia and slime mold Dictyostelium discoideum. These transcription factors recognize a (T/A)TGAC(T/A) cis-regulatory element, also known as a W-box, in the promoters of target genes. WRKY transcription factors play a major role in plant defense to abiotic and biotic stresses, but also contribute to plant development and secondary metabolism. These roles are governed by an ever increasingly complex network of interactions with other DNA-binding and non-DNA-binding proteins.
  • 726
  • 28 Oct 2022
Topic Review
Epigenetic Changes and Chromatin Reorganization in Brain Function
Healthy brain functioning in mammals requires a continuous fine-tuning of gene expression. Accumulating evidence over the past demonstrates that epigenetic mechanisms and dynamic changes in chromatin organization are critical components during the control of gene transcription in neural cells. Genome-wide analyses show that the regulation of brain genes requires the contribution of both promoter and long-distance enhancer elements, which must functionally interact to upregulate gene expression in response to physiological cues. Hence, a deep comprehension of the mechanisms mediating these enhancer–promoter interactions (EPIs) is critical if people are to understand the processes associated with learning, memory and recall. Moreover, the onset and progression of several neurodegenerative diseases and neurological alterations are found to be strongly associated with changes in the components that support and/or modulate the dynamics of these EPIs. 
  • 410
  • 28 Oct 2022
Topic Review
Glutamate-Glutamine Cycle
In biochemistry, the glutamate-glutamine cycle is a sequence of events by which an adequate supply of the neurotransmitter glutamate is maintained in the central nervous system. Neurons are unable to synthesize either the neurotransmitter glutamate or γ-aminobutyric acid (GABA) from glucose. Discoveries of glutamine and glutamate pools within intercellular compartments led to suggestions of the glutamate-glutamine cycle working between neurons and astrocytes. The glutamate/GABA-glutamine cycle is a metabolic pathway that describes the release of glutamate or GABA from neurons which are then taken up into astrocytes (star-shaped glial cells). In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of glutamate or GABA.
  • 470
  • 27 Oct 2022
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