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Topic Review
TPC1 in plants
TPC1 in plants is localized in the vacuolar membrane. Its activity is strictly regulated by several factors emphasizing its complex structure and function. The physiological role of TPC1 is under debate. The TPC1 hyperactive version fou2 (carring D454N mutation) is characterized by an overproduction of jasmonate acid (JA), however the tpc1-2 knockout mutant has no pronounced phenotype. The intriguing concept of Ca2+-induced Ca2+ release was assigned to Vicia faba TPC1 in 1994 by Ward and Schroeder, however it has still not been confirmed for the model plant Arabidopsis thaliana.
  • 906
  • 27 Oct 2020
Topic Review
TNAP in Central Nervous System
Tissue-nonspecific alkaline phosphatase (TNAP) is an ectoenzyme bound to the plasma membranes of numerous cells via a glycosylphosphatidylinositol (GPI) moiety. TNAP is one of many proteins localized to Brain microvascular endothelial cells (BMECs), and is highly abundant in human and rodent cerebral microvessels [33]. There are four alkaline phosphatase (AP) isoenzymes in humans and they include: TNAP, germ cell alkaline phosphatase (GCAP), intestinal alkaline phosphatase (IAP), and placental alkaline phosphatase (PLAP). Although TNAP is ubiquitous in many tissue, it is most highly expressed in bone, liver, intestine, kidney, and brain, while the three other AP isoenzymes are expressed in the tissues for which they are named. TNAP is also highly expressed in cerebral microvessels.
  • 840
  • 10 Jun 2021
Topic Review
Tissue Fibrosis
Tissue fibrosis is characterized by excessive deposition of extracellular matrix (ECM) components that result from the disruption of regulatory processes responsible for ECM synthesis, deposition, and remodeling. Fibrosis develops in response to a trigger or injury and can occur in nearly all organs of the body.
  • 566
  • 29 Oct 2021
Topic Review
Thyroid Disorder and Dizziness in Humans
The regulation of thyroid hormone production is under the control of the hypothalamic–pituitary–thyroid (HPT) axis. TRH (Thyrotropin-Releasing Hormone), which is synthesized and secreted by the neurons of the paraventricular nuclei of the hypothalamus, stimulates the release of TSH (Thyroid-Stimulating Hormone) by the pituitary gland. TSH binds to its membrane receptor in the thyroid follicular cells and triggers the synthesis and secretion of the following thyroid hormones: Thyroxine (Tetraiodothyronine, T4) and T3 (Triiodothyronine). When the concentration of T4 and T3 in the blood increases, a negative feedback loop is set up to inhibit the pituitary response to TRH and decrease TSH secretion.
  • 222
  • 25 Jun 2023
Topic Review
Theory of Addiction
Drug addiction is characterized by a loss of control over drug-seeking and -consumption, despite the profound negative consequences this has on the individual’s life [1]. While the acute effects of a substance depend on its psychoactive properties, the progression of addiction converges into a series of problems that are common and severely impact all spheres of the individual’s life, compromising interpersonal, economic, and health status. Thus, in chronic drug users it is common to present several physical problems including brain damage and atrophy, circulatory system issues, premature aging, among others. From a socio-economic perspective, common problems include homelessness, criminal behavior, unemployment, social isolation, and dependence.
  • 67
  • 01 Feb 2024
Topic Review
The Relationship between Iron and Inflammatory Bowel Diseases
Inflammatory Bowel Diseases, including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic, relapsing inflammatory conditions of the gastrointestinal (GI) tract. Interactions between the environmental factors and commensal intestinal microflora in genetically predisposed individuals are considered the leading cause of an inappropriate immune response and as a result, the development of inflammatory disease. Iron is an indispensable nutrient for life. A lack of it leads to iron deficiency anaemia (IDA), which currently affects about 1.2 billion people worldwide. The primary means of IDA treatment is oral or parenteral iron supplementation. This can be burdened with numerous side effects such as oxidative stress, systemic and local-intestinal inflammation, dysbiosis, carcinogenic processes and gastrointestinal adverse events.
  • 467
  • 15 Sep 2022
Topic Review
The Ponto-Geniculo-Occipital Waves in Dreaming
Rapid eye movement (REM) sleep is the main sleep correlate of dreaming. Ponto-geniculo-occipital (PGO) waves are a signature of REM sleep. They represent the physiological mechanism of REM sleep that specifically limits the processing of external information. PGO waves look just like a message sent from the pons to the lateral geniculate nucleus of the visual thalamus, the occipital cortex, and other areas of the brain. The dedicated visual pathway of PGO waves can be interpreted by the brain as visual information, leading to the visual hallucinosis of dreams. PGO waves are considered to be both a reflection of REM sleep brain activity and causal to dreams due to their stimulation of the cortex. 
  • 220
  • 06 Nov 2023
Topic Review
The PD-1/PD-L1 Pathway
Binding of the immune checkpoint programmed cell death protein 1 (PD-1) to its ligand programmed death-ligand 1 (PD-L1) downregulates the adaptive immune response. PD-L1 is regularly expressed by antigen presenting cells. During an acute immune response, effector T cells transiently upregulate PD-1. In contrast, chronic immune stimulation leads to continuous expression of PD-1 on effector T cells. The latter also occurs in the tumor microenvironment, where PD-L1 can be expressed by tumor cells. The PD-1/PD-L1 pathway is an excellent example for the clinical application of biomarker research in the context of comparative immuno-oncology. Initial comparator studies on this pathway were mainly conducted on cells and tissues derived from mice and humans. This resulted in the discovery of anti PD-1 or anti-PD-L1 immune checkpoint therapy that is widely applied for the treatment of human cancers. The use of monoclonal antibodies directed against PD-1 or PD-L1 as therapeutic agents restores the anti-cancer immune response. In recent years, investigations on these molecules have been extended to canine cancers and confirm the expression of PD-1 and PD-L1 in several canine tumors. Whether immune checkpoint therapy may be a possible treatment option for those canine cancers remains to be revealed in future clinical trials.
  • 650
  • 02 Dec 2022
Topic Review
The Molecular Basis for Zinc Bioavailability
As an essential micronutrient with a nearly ubiquitous presence in nature, zinc is needed for all known aspects of life. Based on the quantification of putative zinc protein binding domains, it is estimated that one-tenth of all human proteins require zinc as a structural element or for an enzyme active site. The structural, catalytic, and regulatory roles of zinc provide the foundation for a broad array of basic cellular functions. Consequently, zinc deficiency affects numerous critical functions, including metabolic, immune, and neurological processes. With zinc nutriture underlying a public health burden of communicable and non-communicable diseases, human zinc deficiency is estimated to be the most prevalent nutrient deficiency worldwide. The etiology of human zinc deficiency has historically been attributed to diets with low zinc bioavailability, e.g., the proportion of dietary zinc available for zinc-dependent functions, with primary attention to diets low in zinc and high in phytic acid.
  • 297
  • 10 Apr 2023
Topic Review
The Microenvironment of the Pathogenesis of Cardiac Hypertrophy
Pathological cardiac hypertrophy is a key risk factor for the development of heart failure and predisposes individuals to cardiac arrhythmia and sudden death. While physiological cardiac hypertrophy is adaptive, hypertrophy resulting from conditions comprising hypertension, aortic stenosis, or genetic mutations, such as hypertrophic cardiomyopathy, is maladaptive. Prolonged cardiovascular stress causes cardiomyocytes and non-myocardial cells to enter an activated state releasing numerous pro-hypertrophic, pro-fibrotic, and pro-inflammatory mediators such as vasoactive hormones, growth factors, and cytokines, i.e., commencing signaling events that collectively cause cardiac hypertrophy. Fibrotic remodeling is mediated by cardiac fibroblasts as the central players, but also endothelial cells and resident and infiltrating immune cells enhance these processes. Many of these hypertrophic mediators are now being integrated into computational models that provide system-level insights and will help to translate our knowledge into new pharmacological targets. 
  • 301
  • 14 Jul 2023
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