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Topic Review
DNA Homeostasis and Senescence
As we age, our bodies accrue damage in the form of DNA mutations. These mutations lead to the generation of sub-optimal proteins, resulting in inadequate cellular homeostasis and senescence. The build-up of senescent cells negatively affects the local cellular micro-environment and drives ageing associated disease, including neurodegeneration. Therefore, limiting the accumulation of DNA damage is essential for healthy neuronal populations.  
  • 616
  • 17 Jun 2021
Topic Review
Chloroplast Trans-Splicing RNA–Protein Supercomplex
In eukaryotes, RNA trans-splicing is a significant RNA modification process for the end-to-end li-gation of exons from separately transcribed primary transcripts to generate mature mRNA. So far, three different categories of RNA trans-splicing have been found in organisms within a diverse range.
  • 616
  • 01 Mar 2021
Topic Review
Iron and Anti-Cancer Immune Response
New insights into the field of iron metabolism within the tumor microenvironment have been uncovered in recent years. Iron promotes the production of reactive oxygen species, which may either trigger ferroptosis cell death or contribute to malignant transformation. Once transformed, cancer cells divert tumor-infiltrating immune cells to satisfy their iron demand, thus affecting the tumor immunosurveillance. In this review, we highlight how the bioavailability of this metal shapes complex metabolic pathways within the tumor microenvironment and how this affects both tumor-associated macrophages and tumor-infiltrating lymphocytes functions. Furthermore, we discuss the potentials as well as the current clinical controversies surrounding the use of iron metabolism as a target for new anticancer treatments in two opposed conditions: (i) the “hot” tumors, which are usually enriched in immune cells infiltration and are extremely rich in iron availability within the microenvironment, and (ii) the “cold” tumors, which are often very poor in immune cells, mainly due to immune exclusion.
  • 616
  • 06 Apr 2021
Topic Review
Factor V Leiden
Factor V Leiden (rs6025 or F5 p.R506Q) is a variant (mutated form) of human factor V (one of several substances that helps blood clot), which causes an increase in blood clotting (hypercoagulability). Due to this mutation, protein C, an anticoagulant protein that normally inhibits the pro-clotting activity of factor V, is not able to bind normally to factor V, leading to a hypercoagulable state, i.e., an increased tendency for the patient to form abnormal and potentially harmful blood clots. Factor V Leiden is the most common hereditary hypercoagulability (prone to clotting) disorder amongst ethnic Europeans. It is named after the Dutch city of Leiden, where it was first identified in 1994 by Rogier Maria Bertina under the direction of (and in the laboratory of) Pieter Hendrick Reitsma. Despite the increased risk of venous thromboembolisms, people with one copy of this gene have not been found to have shorter lives than the general population.
  • 615
  • 07 Nov 2022
Topic Review
Mitochondrial Ca2+ Signaling and Bioenergetics in Alzheimer’s Disease
Alzheimer’s disease (AD) is a hereditary and sporadic neurodegenerative illness defined by the gradual and cumulative loss of neurons in specific brain areas. The processes that cause AD are still under investigation and there are no available therapies to halt it. Progress puts at the forefront the “calcium (Ca2+) hypothesis” as a key AD pathogenic pathway, impacting neuronal, astrocyte and microglial function. An increasing body of evidence points out the early and crucial role of cellular Ca2+ handling dysregulation in AD pathogenesis. Interestingly, Ca2+ is a key regulator of several mitochondrial functions, such as ATP production, and brain cells rely mostly on OXPHOS to match their energy demands.
  • 615
  • 09 Dec 2022
Topic Review
Pluripotency Factor Lin28
Lin28 is an RNA-binding protein that can function as a pluripotency factor and is enriched in stem and progenitor cells and embryonic tissues.  Lin28 can regulate protein synthesis by binding mRNAs to regulate their translation, and by governing microRNA production through binding let-7 family precursor microRNAs to block their processing to mature functional microRNAs.   Lin28 was first discovered in C.elegans and is highly evolutionarily-conserved across the animal kingdom.  In most vertebrates, including mammals, there are two Lin28 paralogs, termed Lin28A and Lin28B.   An appreciation for the complex interactions between the NF-κB transcription factor and the Lin28 RNA binding protein/let-7 microRNA pathways has grown substantially over the past decade.  In many biological settings, accumulated evidence has revealed that Lin28 can be upregulated from low basal levels in adult tissues following injury or in plastic responses. Both the NF-κB and Lin28/let-7 pathways are master regulators impacting cell survival, growth and proliferation, and an understanding of how interfaces between these pathways participate in governing pluripotency, progenitor differentiation, and neuroplastic responses remains an emerging area of research.
  • 614
  • 05 Jan 2021
Topic Review
Protein Structure Prediction
The new advances in deep learning methods have influenced many aspects of scientific research, including the study of the protein system. The prediction of proteins’ 3D structural components is now heavily dependent on machine learning techniques that interpret how protein sequences and their homology govern the inter-residue contacts and structural organization. Especially, methods employing deep neural networks have had a significant impact on recent CASP13 and CASP14 competition. Here, we explore the recent applications of deep learning methods in the protein structure prediction area. We also look at the potential opportunities for deep learning methods to identify unknown protein structures and functions to be discovered and help guide drug–target interactions. Although significant problems still need to be addressed, we expect these techniques in the near future to play crucial roles in protein structural bioinformatics as well as in drug discovery.
  • 613
  • 24 Jun 2021
Topic Review
Skeletal Muscle Extracellular Matrix
The skeletal muscle provides movement and support to the skeleton, controls body temperature, and regulates the glucose level within the body. This is the core tissue of insulin-mediated glucose uptake via glucose transporter type 4 (GLUT4). The extracellular matrix (ECM) provides a scaffold for cells, controlling biological processes, and providing structural as well as mechanical support to surrounding cells. Disruption of ECM homeostasis results in several pathological conditions. Various ECM components are typically found to be augmented in the skeletal muscle of obese and/or diabetic humans. A better understanding of the importance of skeletal muscle ECM remodeling, integrin signaling, and other factors that regulate insulin activity may help in the development of novel therapeutics for managing diabetes and other metabolic disorders.
  • 612
  • 09 Sep 2021
Topic Review
Filaggrin
Filaggrin (FLG) is a large (37-kD), histidine rich protein named after its ability to aggregates keratin intermediate filaments (Filament aggregating Protein). FLG is an important epidermal structural protein, crucial to the structure and function of the stratum corneum (SC) and is largely involved in the maintenance of skin barrier function. FLG deficiency or dysfunction can lead to various skin disorders such as xerosis, ichthyosis vulgaris and atopic dermatitis (AD). It has been proposed that the level of FLG and its degradation products are influenced not only by the FLG loss-of-function mutations but also by endogenous or exogenous factors. 
  • 612
  • 09 Jul 2021
Topic Review
GRP94 in Cancer
Glucose-regulated protein 94 (GRP94) is an endoplasmic reticulum (ER)-resident member of the heat shock protein 90 (HSP90) family. In physiological conditions, it plays a vital role in regulating biological functions, including chaperoning cellular proteins in the ER lumen, maintaining calcium homeostasis, and modulating immune system function. Recently, several reports have shown the functional role and clinical relevance of GRP94 overexpression in the progression and metastasis of several cancers. Therefore, the current review highlights GRP94’s physiological and pathophysiological roles in normal and cancer cells. Additionally, the unmet medical needs of small chemical inhibitors and the current development status of monoclonal antibodies specifically targeting GRP94 will be discussed to emphasize the importance of cell surface GRP94 as an emerging therapeutic target in monoclonal antibody therapy for cancer.
  • 612
  • 11 Oct 2021
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