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Topic Review
Multifunctionality in Microbial Adhesins
Microbial adhesins have multiple functions, and these activities are all evolved and selected. Adhesins can act as enzymes, as assembly scaffolds and components of complex nano-machines. Sometimes, these activities are called secondary because they were discovered secondarily. For instance, microbial type IV pili were first called adhesive. In contrast, phosphoglycerate kinase has its well-known enzymatic activity, but in fungi it also moonlights as an extracellular adhesin.
  • 845
  • 16 Jun 2023
Topic Review
Salivary Volatile Metabolites in Oral Diseases
Oral diseases (ODs) are highly prevalent affecting over 3.5 billion people, particularly in low- and middle-income countries (LMICs). Saliva is often described as the "mirror of the body" and so different omics approaches such us proteomics, metabolomics and more recently, volatomics are being employed to explore the potential of this biofluid towards the non-invasive diagnosis of ODs.
  • 844
  • 30 Nov 2021
Topic Review
ALK+ lung cancer: targeted inhibitors and resistance mechanisms
EML4-ALK is an oncogenic fusion protein that accounts for approximately 5% of non-small cell lung cancer cases. Targeted inhibitors of ALK are now the standard of care treatment often leading to an excellent initial response and increased overall survival. A variety of resistance mechanisms have been identified that eventually lead to relapse highlighting the need for additional treatment options for these patients.
  • 844
  • 01 Aug 2022
Topic Review
Regulation of COX Assembly
Complex IV, or cytochrome c oxidase (COX), is the terminal and probably rate-limiting enzyme of the electron transport chain, responsible for accepting electrons from cytochrome c, pumping protons to contribute to the gradient utilized by ATP synthase to produce ATP, and reducing oxygen to water. As such, COX is tightly regulated through numerous mechanisms including protein–protein interactions.
  • 843
  • 25 Feb 2021
Topic Review
Wnt Signaling Pathway in Liver Metastasis
Liver metastasis, originating either from a primary liver or other cancer types, represent a large cancer-related burden. Therefore, studies that add to better understanding of its molecular basis are needed. Herein, the role of the Wnt signaling pathway in liver metastasis is outlined. Its role in hepatocellular carcinoma (HCC) epithelial-mesenchymal transition (EMT), motility, migration, metastasis formation, and other steps of the metastatic cascade are presented. Additionally, the roles of the Wnt signaling pathway in the liver metastasis formation of colorectal, breast, gastric, lung, melanoma, pancreatic, and prostate cancer are explored.
  • 843
  • 03 Nov 2021
Topic Review
Exosomes in Triple-Negative Breast Cancer
Triple-negative breast cancer (TNBC) is the most potent metastatic type of breast cancer that can spread to other body parts. Chemotherapy and surgical intervention are the sole treatments for TNBC, owing to the scarcity of therapeutic targets. Manipulation of the membranes as per the desired targets of exosomes has recently gained much attention as a drug delivery method. 
  • 843
  • 28 Feb 2023
Topic Review
New Horizons in Structural Biology of Membrane Proteins
A third of both pro- and eukaryotic proteomes consist of membrane proteins. Housed in a milieu of hydrophobic molecules, they serve as crucial contacts of communication between the cytoplasm and non-cytosolic environments, making them essential pharmaceutical targets. While membrane proteins are notoriously difficult to investigate at any level, high-resolution structures of these targets only became feasible at the very end of the twentieth century. It was not until robust technological developments in the fields of X-ray crystallography, NMR spectroscopy and cryo-EM, that the scientific community at large, finally gained access to an ever-increasing number of atomic resolution structures, and began to rationalize how membrane proteins accommodate their function. As if the lack of structural information wasn’t enough to hamper progress, a higher level of complexity arose from the modern understanding of “one structure—one function” paradigm, a primitive simplification useful at the dawn of the scientific era, that has promptly lost credence to the complex maneuvers of membrane proteins.
  • 842
  • 26 Apr 2022
Topic Review
Auxin's Role in Nitrate-Regulated Plant Growth and Development
As a major component of vital macromolecules such as nucleic acids, amino acids, and chlorophyll, nitrogen is an essential macronutrient for plants. Although nitrogen is one of the most abundant elements in nature, accounting for about 70% of atmospheric gasses, its availability for plant uptake in the soil varies temporally and spatially. Therefore, modern agriculture relies heavily on nitrogen fertilization to maximize crop quality and yield. Auxins are a group of naturally occurring molecules derived from tryptophan, with indole-3-acetic acid (IAA) being the major form of auxin. The biosynthesis of IAA is defined by a two-step metabolic pathway, in which the TAA family of aminotransferases converts tryptophan (Trp) to indole-3-pyruvate (IPA), followed by a YUC flavin monooxygenases-mediated conversion of IPA to IAA. Auxin has extensive regulatory functions in plant development. 
  • 842
  • 10 Jul 2023
Topic Review
Metal Ion-Directed Specific DNA Structures
Various DNA structures, including specific metal ion complexes, have been designed based on the knowledge of canonical base pairing as well as general coordination chemistry. The role of metal ions in these studies is quite broad and diverse. Metal ions can be targets themselves in analytical applications, essential building blocks of certain DNA structures that one wishes to construct, or they can be responsible for signal generation, such as luminescence or redox. 
  • 841
  • 29 Jun 2022
Topic Review
Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization
Hsp90 is a ubiquitous molecular chaperone involved in many cell signaling pathways, and its interactions with specific chaperones and cochaperones determines which client proteins to fold. Hsp90 has been shown to be involved in the promotion and maintenance of proper protein complex assembly either alone or in association with other chaperones such as the R2TP chaperone complex. Hsp90-R2TP acts through several mechanisms, such as by controlling the transcription of protein complex subunits, stabilizing protein subcomplexes before their incorporation into the entire complex, and by recruiting adaptors that facilitate complex assembly.
  • 841
  • 05 Aug 2022
Topic Review
Metabolism and Bone Diseases
Bone, a highly mineralized organ that serves as a skeleton of the body, is continuously depositing and resorbing bone matrix to maintain homeostasis. This highly coordinated event is regulated throughout life by bone cells such as osteoblasts, osteoclasts, and osteocytes, and requires synchronized activities from different metabolic pathways. The dysregulation of these metabolic pathways leads to bone disorders.
  • 840
  • 30 Dec 2020
Topic Review
THUMP-Related tRNA Modification Enzymes
The existence of the thiouridine synthetase, methyltransferase and pseudouridine synthase (THUMP) domain was originally predicted by a bioinformatic study. Since the prediction of the THUMP domain, many tRNA modification enzymes containing the THUMP domain have been identified. According to their enzymatic activity, THUMP-related tRNA modification enzymes can be classified into five types, namely 4-thiouridine synthetase, deaminase, methyltransferase, a partner protein of acetyltransferase and pseudouridine synthase. Biochemical, biophysical and structural studies of tRNA 4-thiouridine synthetase, tRNA methyltransferases and tRNA deaminase have established the concept that the THUMP domain captures the 3′-end of RNA (in the case of tRNA, the CCA-terminus).
  • 839
  • 15 Feb 2023
Topic Review
Amino Acids and Its Roles in Glioma Pathology
Amino acids (AAs) are indispensable building blocks of diverse bio-macromolecules as well as functional regulators for various metabolic processes. The fact that cancer cells live with a voracious appetite for specific AAs has been widely recognized. Glioma is one of the most lethal malignancies occurring in the central nervous system. The reprogrammed metabolism of AAs benefits glioma proliferation, signal transduction, epigenetic modification, and stress tolerance. Metabolic alteration of specific AAs also contributes to glioma immune escape and chemoresistance. For clinical consideration, fluctuations in the concentrations of AAs observed in specific body fluids provides opportunities to develop new diagnosis and prognosis markers.
  • 838
  • 14 Oct 2022
Topic Review
CCCTC-Binding Factor for Chromatin Regulation
Chromatin, a macromolecular complex of DNA, RNA, and proteins, provides a framework for the packaging of genetic material within the cell nucleus. Its organization plays a crucial role in gene expression and is regulated by a diverse array of protein complexes in response to a dynamic code of histone posttranslational modifications and DNA modifications. Architectural proteins are essential epigenetic regulators that play a critical role in organizing chromatin and controlling gene expression. CTCF (CCCTC-binding factor) is a key architectural protein responsible for maintaining the intricate 3D structure of chromatin. Because of its multivalent properties and plasticity to bind various sequences, CTCF is similar to a Swiss knife for genome organization.
  • 838
  • 25 May 2023
Topic Review
E3 Ubiquitin Ligase TRIP12
The Thyroid hormone Receptor Interacting Protein 12 (TRIP12) protein belongs to the 28-member Homologous to the E6-AP C-Terminus (HECT) E3 ubiquitin ligase family. First described as an interactor of the thyroid hormone receptor, TRIP12’s biological importance was revealed by the embryonic lethality of a murine model bearing an inactivating mutation in the TRIP12 gene. Further studies showed the participation of TRIP12 in the regulation of major biological processes such as cell cycle progression, DNA damage repair, chromatin remodeling, and cell differentiation by an ubiquitination-mediated degradation of key protein substrates. Moreover, alterations of TRIP12 expression have been reported in cancers that can serve as predictive markers of therapeutic response. The TRIP12 gene is also referenced as a causative gene associated to intellectual disorders such as Clark–Baraitser syndrome and is clearly implicated in Autism Spectrum Disorder. The aim of the review is to provide an exhaustive and integrated overview of the different aspects of TRIP12 ranging from its regulation, molecular functions and physio-pathological implications.
  • 837
  • 23 Nov 2020
Topic Review
Interleukin-4 Promotes Acetylcholine Production
Tuft cells are taste-like chemosensory cells found in the intestinal epithelium involved in the activation of group 2 innate lymphoid cells (ILC2). Although tuft cells in other tissues secrete the neurotransmitter acetylcholine (ACh), their function in the gut remains poorly understood. We investigated changes in the expression of genes and cell differentiation of the intestinal epithelium by stimulation with interleukin-4 (IL-4) or IL-13 in macaque intestinal organoids. This study is the first to demonstrate ACh upregulation by IL-4 induction in primates, suggesting that IL-4 plays a role in Paneth cell granule secretion via paracrine stimulation.
  • 836
  • 25 Aug 2021
Topic Review
TOR–PKA Interactions
TOR and PKA signaling are the major growth-regulatory nutrient-sensing pathways in S. cerevisiae. A number of experimental findings demonstrated a close relationship between these pathways: Both are responsive to glucose availability. Both regulate ribosome production on the transcriptional level and repress autophagy and the cellular stress response. Sch9, a major downstream effector of TORC1 presumably shares its kinase consensus motif with PKA, and genetic rescue and synthetic defects between PKA and Sch9 have been known for a long time.
  • 836
  • 16 Feb 2022
Topic Review
Circadian Oscillations in Skin
The term circadian rhythm, defined by Franz Halberg, a pioneer of chronobiology, in 1959, was originally adapted from Greek. It is a hybrid of the words “circa” and “day”, meaning approximately 24 h or a day. In his later work, Halberg described biological cycles, which are an overlay of oscillations that occur in mammals. Circadian rhythm is closely linked to immunological processes and skin homeostasis, and its desynchrony can be linked to the perturbation of the skin. The interplay between circadian rhythm and annual, seasonal oscillations, as well as the impact of these periodic events on the skin, is described.
  • 835
  • 31 Mar 2023
Topic Review
Hippo Signaling in Fibrotic Diseases
Fibrosis results from defective wound healing processes often seen after chronic injury and/or inflammation in a range of organs. Progressive fibrotic events may lead to permanent organ damage/failure. The hallmark of fibrosis is the excessive accumulation of extracellular matrix (ECM), mostly produced by pathological myofibroblasts and myofibroblast-like cells. The Hippo signaling pathway is an evolutionarily conserved kinase cascade, which has been described well for its crucial role in cell proliferation, apoptosis, cell fate decisions, and stem cell self-renewal during development, homeostasis, and tissue regeneration.
  • 835
  • 14 Jul 2022
Topic Review
Antitumor Drugs and Their Targets
Through novel methodologies, including both basic and clinical research, progress has been made in the therapy of solid cancer. Recent innovations in anticancer therapies, including immune checkpoint inhibitor biologics, therapeutic vaccines, small drugs, and CAR-T cell injections, mark a new epoch in cancer research, already known for faster (epi-)genomics, transcriptomics, and proteomics. As the long-sought after personalization of cancer therapies comes to fruition, the need to evaluate all current therapeutic possibilities and select the best for each patient is of paramount importance. This is a novel task for medical care that deserves prominence in therapeutic considerations in the future. This is because cancer is a complex genetic disease. In its deadly form, metastatic cancer, it includes altered genes (and their regulators) that encode ten hallmarks of cancer-independent growth, dodging apoptosis, immortalization, multidrug resistance, neovascularization, invasiveness, genome instability, inflammation, deregulation of metabolism, and avoidance of destruction by the immune system. These factors have been known targets for many anticancer drugs and treatments, and their modulation is a therapeutic goal, with the hope of rendering solid cancer a chronic rather than deadly disease. In this article, the current therapeutic arsenal against cancers is reviewed with a focus on immunotherapies.
  • 834
  • 19 Aug 2021
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