Topic Review
Tendon and Mast Cells
Understanding the links between the tendon healing process, inflammatory mechanisms, and tendon homeostasis after tissue damage is crucial in developing novel therapeutics for human tendon disorders. The inflammatory mechanisms that are operative in response to tendon injury are not fully understood, but it has been suggested that inflammation occurring in response to nerve signaling, i.e., neurogenic inflammation, has a pathogenic role. In this review, we discuss the role of mast cells in the communication with peripheral nerves, and their emerging role in tendon healing and inflammation after injury.
  • 957
  • 29 Oct 2020
Topic Review
Temozolomide Use in IDH-Mutant Gliomas
In this entry, we discuss the use of the alkylating agent temozolomide (TMZ) in the treatment of IDH-mutant gliomas. We describe the challenges associated with TMZ in clinical (drug resistance and tumor recurrence) and preclinical settings (variabilities associated with in vitro models) in treating IDH-mutant glioma.
  • 694
  • 03 Jun 2021
Topic Review
Telomeres
To survive and reproduce, living organisms must maintain homeostasis both in unchallenged (normal) and challenged (stressful) contexts. This requires the evolution of powerful stress response mechanisms adapted to a particular ecosystem and to regular environmental fluctuations. Thus, these mechanisms may be very diverse within the tree of life. The pioneering work of Miroslav Radman on the stress response in bacteria demonstrated the rapid and adaptive value of changing mutation rates for rapid evolution (the mutator effect). In other words, to facilitate the survival of a species, whether it be to respond to a replication blockade or to a stressful environment, it is better to rapidly evolve by generating more mutations, some being possibly lethal, than to die immediately. We believe that this principle applies to the complex dynamics of telomeres in eukaryotes, which become altered in response to stress.
  • 700
  • 02 Jun 2021
Topic Review
Telomere-Binding Protein
Telomere-binding proteins (also known as TERF, TRBF, TRF) function to bind telomeric DNA in various species. In particular, telomere-binding protein refers to TTAGGG repeat binding factor-1 (TRF1) and TTAGGG repeat binding factor-2 (TRF2). Telomere sequences in humans are composed of TTAGGG sequences which provide protection and replication of chromosome ends to prevent degradation. Telomere-binding proteins can generate a T-loop to protect chromosome ends. TRFs are double-stranded proteins which are known to induce bending, looping, and pairing of DNA which aids in the formation of T-loops. They directly bind to TTAGGG repeat sequence in the DNA. There are also subtelomeric regions present for regulation. However, in humans, there are six subunits forming a complex known as shelterin.
  • 387
  • 16 Nov 2022
Topic Review
Telomere Length and Male Fertility
Telomeres are evolutionary conserved,  multifunctional  DNA-protein complexes located at the ends of eukaryotic chromosomes. Infertility is the inability of a couple to conceive naturally after one year of regular unprotected sexual intercourse.  Male infertility is a complex multifactorial pathological condition with profoundly different phenotypic presentations. Lifestyle factors, genetics, and telomeres are associated with male infertility. A moderate involvement of telomere length in male infertility and SNPs to be pleiotropic and to be involved in other regulatory mechanisms independent from telomere homeostasis, but involved in the spermatogenic process.
  • 443
  • 18 May 2021
Topic Review
Telocytes in the Female Reproductive System
Telocytes (TCs) have been described in the ovary, uterine tubes, uterus, vagina, mammary gland, and placenta. Their morphological features, immunophenotype, physiological functions, and roles in disease have been thoroughly documented in both animal models and human subjects. TCs, with their extremely long cytoplasmic processes called telopodes, play a pivotal role in the morphological and functional interconnection of all the components of the interstitial compartment, but also with constituents of the parenchyma.
  • 399
  • 07 Mar 2022
Topic Review
Telocytes in Modulating Gut Motility Function and Development
Telocytes (TCs) are interstitial cells with distinct features. They have extensions that react to mechanical stimulation through calcium channels. The ability of TCs to communicate with surrounding cells, especially stem cells (SCs), through gap junctions and extracellular vesicles opens a wide range of questions. Moreover, the hypothesis that TCs are capable of carrying out the cellular niche for stem cell regulation and support suggests that TCs could play an important part in the response to major changes in homeostasis. It also suggests that TCs have a significant functional role in tissues that have an increased turnover.
  • 236
  • 25 Sep 2023
Topic Review
Techniques to Preserve Endothelial Cells in Vein Grafts
Endothelial cells comprise the intimal layer of the vasculature, playing a crucial role in facilitating and regulating aspects such nutrient transport, vascular homeostasis, and inflammatory response. Endothelial dysfunction is believed to be a key driver for vein graft disease—a pathology in which vein grafts utilised in coronary artery bypass graft surgery develop intimal hyperplasia and accelerated atherosclerosis, resulting in poor long-term patency rates. Activation and denudation of the endothelium following surgical trauma and implantation of the graft encourage a host of immune, inflammatory, and cellular differentiation responses that risk driving the graft to failure. Several approaches have been developed to mitigate the onset and progression of this pathology both clincally and surgically, including optimisation of surgical technique, vein preservation conditions and pharma-modulation. Novel approaches are also under investigation in recent years, including the use of topical gene therapy and the utilisation of endothelial progenitor/colony-forming cells to regenerate vein grafts with the view to improving patient outcomes.
  • 479
  • 10 Oct 2022
Topic Review Peer Reviewed
Techniques for Theoretical Prediction of Immunogenic Peptides
Small peptides are an important component of the vertebrate immune system. They are important molecules for distinguishing proteins that originate in the host from proteins derived from a pathogenic organism, such as a virus or bacterium. Consequently, these peptides are central for the vertebrate host response to intracellular and extracellular pathogens. Computational models for prediction of these peptides have been based on a narrow sample of data with an emphasis on the position and chemical properties of the amino acids. In past literature, this approach has resulted in higher predictability than models that rely on the geometrical arrangement of atoms. However, protein structure data from experiment and theory are a source for building models at scale, and, therefore, knowledge on the role of small peptides and their immunogenicity in the vertebrate immune system. The following sections introduce procedures that contribute to theoretical prediction of peptides and their role in immunogenicity. Lastly, deep learning is discussed as it applies to immunogenetics and the acceleration of knowledge by a capability for modeling the complexity of natural phenomena.
  • 396
  • 20 Mar 2024
Topic Review
TDP-43 Role in Chromatin Remodeling and Transcription
TDP-43 gained momentum in the neurodegeneration field when it was first discovered that almost all amyotrophic lateral sclerosis (ALS) cases and as many as half of frontotemporal dementia (FTD) cases present pathological ubiquitinated inclusions of TDP-43. Its involvement in chromatin silencing and nuclear/cytoplasmic shuttling constitute convergent key findings from several biological screens, and several crucial epigenetic factors appear to be able to modify TDP-43-induced degeneration. TDP-43 activity at the chromatin level and its implication in the regulation of DNA transcription and stability -such as DNA repair and regulation of retrotransposons activity- are further supported by a continuously growing amount of studies.
  • 543
  • 19 Sep 2023
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