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Topic Review
T5SS and Other Secretion Systems in Bacteria
Bacteria have existed on Earth for billions of years, exhibiting ubiquity and involvement in various biological activities. To ensure survival, bacteria usually release and secrete effector proteins to acquire nutrients and compete with other microorganisms for living space during long-term evolution. Consequently, bacteria have developed a range of secretion systems, which are complex macromolecular transport machines responsible for transporting proteins across the bacterial cell membranes. Among them, one particular secretion system that stands out from the rest is the type V secretion system (T5SS), known as the “autotransporter”.
  • 361
  • 27 Dec 2023
Topic Review
T2DM and the Gut Microbiota
Type 2 Diabetes Mellitus (T2DM) affects over 9% of the United States population alone, constitutes a cause for ensuing cardiovascular disease, and is typically closely linked to obesity status. While obesity has long been perceived to stem from a sedentary lifestyle and high fat intake there is increasing evidence supporting the idea that this is a more complex issue than initially thought. The human gut microbiome has been a recent point of investigation due to the idea that it may be closely linked to T2DM. The aforementioned high fat diets can impact the gut microbiome in a significant way, altering the demography of the gut’s microflora, hence shifting the gut into a state of dysbiosis. Dysbiosis is a state that favors the initiation of a cascade inducing metabolic deregulation, increasing inflammation and insulin resistance systemically. Below the relationship of the microbiome to T2DM is briefly discussed.
  • 1.3K
  • 29 Oct 2020
Topic Review
T2Candida
Invasive candidiasis is a common healthcare-associated infection with high mortality and is difficult to diagnose due to nonspecific symptoms and limitations of culture based diagnostic methods. T2Candida, based on T2 magnetic resonance technology, is FDA approved for the diagnosis of candidemia and can rapidly detect the five most commonly isolated Candida sp. in approximately 5 h directly from whole blood. We discuss the preclinical and clinical studies of T2Candida for the diagnosis of candidemia and review the current literature on its use in deep-seated candidiasis, its role in patient management and prognosis, clinical utility in unique populations and non-blood specimens, and as an antifungal stewardship tool. Lastly, we summarize the strengths and limitations of this promising nonculture-based diagnostic test.
  • 505
  • 09 Mar 2021
Topic Review
T(8;21) Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a heterogenous disease with multiple sub-types which are defined by different somatic mutations that cause blood cell differentiation to go astray.  One of the best-studied AML-subtypes is the t(8;21) AML which carries a translocation fusing sequences encoding the DNA-binding domain of the hematopoietic master regulator RUNX1 to the ETO gene. 
  • 674
  • 13 Jan 2021
Topic Review
T-Cell Receptor Signalosome
Human immunodeficiency virus type-1 (HIV-1) can undergo either a lytic pathway to cause productive systemic infection or enter a latent state in which the integrated provirus remains transcriptionally silent for decades. The ability to latently infected T-cells enables HIV-1 to establish persistent infections in resting memory CD4+ T-lymphocytes which become reactivated following disruption or cessation of intensive drug therapy. Maintenance of viral latency occurs through epigenetic and non-epigenetic mechanisms. Epigenetic mechanisms of HIV latency regulation involve deacetylation and methylation of histone proteins within Nucleosome 1 (nuc -1) at the viral long terminal repeats (LTR) such that inhibition of histone deacetyltransferase and histone lysine methyltransferase activities, respectively, reactivates HIV from latency. Non-epigenetic mechanisms involve nuclear restriction of critical cellular transcription factors such as Nuclear factor-kappa Beta (NF-kB) or Nuclear factor of activated T-cells (NFAT) which activate transcription from the viral LTR, limiting nuclear levels of viral transcription transactivator protein Tat and its cellular co-factor; positive transcription elongation factor b (P-TEFb) which together regulate HIV transcriptional elongation. The T-cell receptor (TCR) activation efficiently induces NF-kB, NFAT, and activator protein 1 (AP-1) transcription factors through multiple signal pathways and how these factors efficiently regulate HIV LTR transcription through the non-epigenetic mechanism. Elongation factor P-TEFb induced through an extracellular signal-regulated kinase (ERK) dependent mechanism regulates HIV transcriptional elongation before Tat is synthesized and the role of AP-1 in the modulation of HIV transcriptional elongation through functional synergy with NF-kB. The TCR signaling induces critical posttranslational modifications of the Cyclin-dependent kinase 9 (CDK9) subunit of P-TEFb which enhances interactions between P-TEFb and viral Tat protein and the resultant enhancement of HIV transcriptional elongation.
  • 830
  • 13 Aug 2020
Topic Review
T-Cell Receptor Repertoire Sequencing and Its Applications
The immune system is a dynamic feature of each individual and a footprint of our unique internal and external exposures. Indeed, the type and level of exposure to physical and biological agents shape the development and behavior of this complex and diffuse system. Many pathological conditions depend on how our immune system responds or does not respond to a pathogen or a disease or on how the regulation of immunity is altered by the disease itself. T-cells are important players in adaptive immunity and, together with B-cells, define specificity and monitor the internal and external signals that our organism perceives through its specific receptors, TCRs and BCRs, respectively. Today, high-throughput sequencing (HTS) applied to the TCR repertoire has opened a window of opportunity to disclose T-cell repertoire development and behavior down to the clonal level. Although TCR repertoire sequencing is easily accessible today, it is important to deeply understand the available technologies for choosing the best fit for the specific experimental needs and questions. Here, an updated overview of TCR repertoire sequencing strategies, providers and applications to infectious diseases and cancer to guide researchers’ choice through the multitude of available options is provided. The possibility of extending the TCR repertoire to HLA characterization will be of pivotal importance in the near future to understand how specific HLA genes shape T-cell responses in different pathological contexts and will add a level of comprehension that was unthinkable just a few years ago.
  • 1.2K
  • 24 Aug 2022
Topic Review
T-Cell Intracellular Antigen 1
T-cell intracellular antigen 1 (TIA1) is an RNA-binding protein that is expressed in many tissues and in the vast majority of species, although it was first discovered as a component of human cytotoxic T lymphocytes. TIA1 has a dual localization in the nucleus and cytoplasm, where it plays an important role as a regulator of gene-expression flux. As a multifunctional master modulator, TIA1 controls biological processes relevant to the physiological functioning of the organism and the development and/or progression of several human pathologies. 
  • 390
  • 10 Mar 2022
Topic Review
T-Cell Acute Lymphoblastic Leukemia
Thanks to the use of high-resolution genetic techniques to detect cryptic aberrations present in T-ALL, researchers now have a clearer view of the genetic landscape that explains the particular oncogenetic processes taking place in each T-ALL. They also have begun to understand relapse-specific mechanisms. To summarize the latest advances in the knowledge of the genome in T-ALL and highlight the areas where the research on this ALL subtype is progressing, thereby identifying the key issues that need to be addressed in the medium-to-long term to move forward in the applicability of this knowledge into clinics.
  • 854
  • 02 Jun 2022
Topic Review
T-2054
Osteoarthritis (OA), a degenerative joint disorder, has been reported as the most common cause of disability worldwide. The production of inflammatory cytokines is the main factor in OA. Previous studies have been reported that obeticholic acid (OCA) and OCA derivatives inhibited the release of proinflammatory cytokines in acute liver failure, but they have not been studied in the progression of OA. In our study, we screened our small synthetic library of OCA derivatives and found T-2054 had anti-inflammatory properties.
  • 556
  • 06 May 2021
Topic Review
T regulatory cell (Treg)
Regulatory T cells (Tregs) are a subset of CD4+ T lymphocytes that possesses the capacity to suppress immune responses to ensure that the immune system’s response to foreign antigens and its response to self-antigens remains adequately balanced. This homeostatic balance ensures the immune system is inflammatory enough to respond sufficiently to foreign antigens, as well as neoantigens from cancer, and sufficiently counter-balanced or anti-inflammatory that inflammation does not get out of hand, leading to tissue damage or death. The immune-suppressive effects of Tregs regulate tumor immunity, antimicrobial resistance, allergy and transplantation. Tregs also play a central role in maintaining self-tolerance. Treg involvement in this mechanism is pivotal for protection from autoimmune diseases.
  • 747
  • 26 Oct 2020
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