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Topic Review
Anaplasma Species in Africa
Anaplasma species, belonging to the family Anaplasmataceae in the order Rickettsiales, are obligate intracellular bacteria responsible for various tick-borne diseases of veterinary and human significance worldwide. With advancements in molecular techniques, seven formal species of Anaplasma and numerous unclassified species have been described. In Africa, several Anaplasma species and strains have been identified in different animals and tick species
  • 732
  • 18 May 2023
Topic Review
Mitochondrial Bioenergetics in the Regulation of Neurogenesis
Mitochondria, far beyond their prominent role as cellular powerhouses, are complex cellular organelles active as central metabolic hubs that are capable of integrating and controlling several signaling pathways essential for neurological processes, including neurogenesis and neuroplasticity. On the other hand, mitochondria are themselves regulated from a series of signaling proteins to achieve the best efficiency in producing energy, in establishing a network and in performing their own de novo synthesis or clearance. Dysfunctions in signaling processes that control mitochondrial biogenesis, dynamics and bioenergetics are increasingly associated with impairment in brain development and involved in a wide variety of neurodevelopmental disorders. 
  • 732
  • 29 Aug 2023
Topic Review
RPA Phosphorylation in DNA Double-Strand Break Repair
Human Replication Protein A (RPA) was historically discovered as one of the six components needed to reconstitute simian virus 40 DNA replication from purified components. RPA is now known to be involved in all DNA metabolism pathways that involve single-stranded DNA (ssDNA). Heterotrimeric RPA comprises several domains connected by flexible linkers and is heavily regulated by post-translational modifications (PTMs). The structure of RPA has been challenging to obtain. Various structural methods have been applied, but a complete understanding of RPA’s flexible structure, its function, and how it is regulated by PTMs has yet to be obtained.
  • 731
  • 19 Feb 2024
Topic Review
Transcriptional Enhancers in Cancer
One of the major challenges in cancer treatments is the dynamic adaptation of tumor cells to cancer therapies. In this regard, tumor cells can modify their response to environmental cues without altering their DNA sequence. This cell plasticity enables cells to undergo morphological and functional changes, for example, during the process of tumour metastasis or when acquiring resistance to cancer therapies. Central to cell plasticity, are the dynamic changes in gene expression that are controlled by a set of molecular switches called enhancers. Enhancers are DNA elements that determine when, where and to what extent genes should be switched on and off. Thus, defects in enhancer function can disrupt the gene expression program and can lead to tumour formation. Here, we review how enhancers control the activity of cancer-associated genes and how defects in these regulatory elements contribute to cell plasticity in cancer. Understanding enhancer (de)regulation can provide new strategies for modulating cell plasticity in tumour cells and can open new research avenues for cancer therapy. 
  • 730
  • 23 Aug 2021
Topic Review
ECM Biomarkers in Colorectal Cancer
The cellular microenvironment composition and changes therein play an extremely important role in cancer development. Changes in the extracellular matrix (ECM), which constitutes a majority of the tumor stroma, significantly contribute to the development of the tumor microenvironment. These alterations within the ECM and formation of the tumor microenvironment ultimately lead to tumor development, invasion, and metastasis. The ECM is composed of various molecules such as collagen, elastin, laminin, fibronectin, and the MMPs that cleave these protein fibers and play a central role in tissue remodeling. When healthy cells undergo an insult like DNA damage and become cancerous, if the ECM does not support these neoplastic cells, further development, invasion, and metastasis fail to occur. Therefore, ECM-related cancer research is indispensable, and ECM components can be useful biomarkers as well as therapeutic targets. Colorectal cancer specifically, is also affected by the ECM and many studies have been conducted to unravel the complex association between the two
  • 730
  • 08 Sep 2021
Topic Review
Chromatin Accessibility Regulates White-Opaque Switching
Candida albicans, a diploid polymorphic fungus, has evolved a unique heritable epigenetic program that enables reversible phenotypic switching between two cell types, referred to as “white” and “opaque”. These cell types are established and maintained by distinct transcriptional programs that lead to differences in metabolic preferences, mating competencies, cellular morphologies, responses to environmental signals, interactions with the host innate immune system, and expression of approximately 20% of genes in the genome. Transcription factors that regulate the establishment and heritable maintenance of the white and opaque cell types have been a primary focus of investigation in the field; however, other factors that impact chromatin accessibility, such as histone modifying enzymes, chromatin remodelers, and histone chaperone complexes, also modulate the dynamics of the white-opaque switch and have beenmuch less studied to date.
  • 729
  • 05 Feb 2021
Topic Review
Arsenite Inducible Regulatory Particle-Associate Protein
Maintaining 26S proteasome activity under diverse physiological conditions is a fundamental requirement in order to maintain cellular proteostasis. Several quantitative and qualitative mechanisms have evolved to ensure that ubiquitin–proteasome system (UPS) substrates do not accumulate and lead to promiscuous protein–protein interactions that, in turn, lead to cellular malfunction.
  • 729
  • 30 Sep 2021
Topic Review
Anticancer Strategies Targeting JWA
JWA is a microtubule-associated protein and an environmental response gene. JWA has been identified as a potential therapeutic target for several cancers. 
  • 729
  • 08 Oct 2022
Topic Review
Identification of DNA G-Guadruplexes
DNA G-quadruplexes (G4s) are non-canonical secondary structures formed in guanine-rich sequences. Within the human genome, G4s are found in regulatory regions such as gene promoters and telomeres to control replication, transcription, and telomere lengthening. In the cellular context, there are several proteins named as G4-binding proteins (G4BPs) that interact with G4s, either anchoring upon, stabilizing, and/or unwinding them.
  • 729
  • 08 Feb 2023
Topic Review
Inflammasomes and Hematopoietic Homeostasis
Hematopoietic stem cells (HSCs) regularly produce various blood cells throughout life via their self-renewal, proliferation, and differentiation abilities. Most HSCs remain quiescent in the bone marrow (BM) and respond in a timely manner to either physiological or pathological cues, but the underlying mechanisms remain to be further elucidated. In the past few years, accumulating evidence has highlighted an intermediate role of inflammasome activation in hematopoietic maintenance, post-hematopoietic transplantation complications, and senescence. As a cytosolic protein complex, the inflammasome participates in immune responses by generating a caspase cascade and inducing cytokine secretion. This process is generally triggered by signals from purinergic receptors that integrate extracellular stimuli such as the metabolic factor ATP via P2 receptors. Furthermore, targeted modulation/inhibition of specific inflammasomes may help to maintain/restore adequate hematopoietic homeostasis.
  • 728
  • 07 Feb 2021
Topic Review
Antioxidant Therapies in TBI
Due to a multiplicity of causes provoking traumatic brain injury (TBI), TBI is a highly heterogeneous pathology, characterized by high mortality and disability rates. TBI is an acute neurodegenerative event, potentially and unpredictably evolving into sub-chronic and chronic neurodegenerative events, with transient or permanent neurologic, cognitive, and motor deficits, for which no valid standardized therapies are available. A vast body of literature demonstrates that TBI-induced oxidative/nitrosative stress is involved in the development of both acute and chronic neurodegenerative disorders. Cellular defenses against this phenomenon are largely dependent on low molecular weight antioxidants, most of which are consumed with diet or as nutraceutical supplements. A large number of studies have evaluated the efficacy of antioxidant administration to decrease TBI-associated damage in various animal TBI models and in a limited number of clinical trials. Points of weakness of preclinical studies are represented by the large variability in the TBI model adopted, in the antioxidant tested, in the timing, dosages, and routes of administration used, and in the variety of molecular and/or neurocognitive parameters evaluated. The analysis of the very few clinical studies does not allow strong conclusions to be drawn on the real effectiveness of antioxidant administration to TBI patients. Standardizing TBI models and different experimental conditions, as well as testing the efficacy of administration of a cocktail of antioxidants rather than only one, should be mandatory. According to some promising clinical results, it appears that sports-related concussion is probably the best type of TBI to test benefits of antioxidant administration.
  • 728
  • 08 Apr 2021
Topic Review
Genome-Folding Mechanisms in the Tree Domains of Life
Comparative structural/molecular biology by single-molecule analyses combined with single-cell dissection, mass spectroscopy, and biochemical reconstitution have been powerful tools for elucidating the mechanisms underlying genome DNA folding. All genomes in the three domains of life undergo stepwise folding from DNA to 30–40 nm fibers. Major protein players are histone (Eukarya and Archaea), Alba (Archaea), and HU (Bacteria) for fundamental structural units of the genome. In Euryarchaeota, a major archaeal phylum, either histone or HTa (the bacterial HU homolog) were found to wrap DNA. This finding divides archaea into two groups: those that use DNA-wrapping as the fundamental step in genome folding and those that do not. Archaeal transcription factor-like protein TrmBL2 has been suggested to be involved in genome folding and repression of horizontally acquired genes, similar to bacterial H-NS protein. Evolutionarily divergent SMC proteins contribute to the establishment of higher-order structures. Recent results are presented, including the use of Hi-C technology to reveal that archaeal SMC proteins are involved in higher-order genome folding, and the use of single-molecule tracking to reveal the detailed functions of bacterial and eukaryotic SMC proteins. Here, we highlight the similarities and differences in the DNA-folding mechanisms in the three domains of life. 
  • 728
  • 28 Dec 2021
Topic Review
Domain Composition of MAST Kinases
Microtubule-Associated Serine/Threonine (MAST) kinases represent an evolutionary conserved branch of the AGC protein kinase superfamily in the kinome. Since the discovery of the founding member, MAST2, in 1993, three additional family members have been identified in mammals and found to be broadly expressed across various tissues, including the brain, heart, lung, liver, intestine and kidney.
  • 728
  • 03 Aug 2023
Topic Review
Immune cell response during Sepsis
Sepsis is a life-threatening medical condition that occurs when the host has an uncontrolled or abnormal immune response to overwhelming infection. It is now widely accepted that sepsis occurs in two concurrent phases, which consist of an initial immune activation phase followed by a chronic immunosuppressive phase, leading to immune cell death. Depending on the severity of the disease and the pathogen involved, the hosts immune system may not fully recover, leading to ongoing complications proceeding the initial infection. As such, sepsis remains one of the leading causes of morbidity and mortality world-wide, with treatment options limited to general treatment in intensive care units (ICU). Lack of specific treatments available for sepsis is mostly due to our limited knowledge of the immuno-physiology associated with the disease. This review will provide a comprehensive overview of the mechanisms and cell types involved in eliciting infection-induced immune activation from both the innate and adaptive immune system during sepsis. In addition, the mechanisms leading to immune cell death following hyperactivation of immune cells will be explored. The evaluation and better understanding of the cellular and systemic responses leading to disease onset could eventuate into the development of much needed therapies to combat this unrelenting disease. 
  • 727
  • 05 Aug 2021
Topic Review
Metabolic Phenotype Alterations in AN through Metabolomics
Anorexia nervosa (AN) is a mental disorder characterized by an intense fear of weight gain that affects mainly young women. It courses with a negative body image leading to altered eating behaviors that have devastating physical, metabolic, and psychological consequences for the patients. Metabolomics is the comprehensive analysis of the metabolites included in a specific biological compartment at a specific time (metabolome). Metabolomics is proposed as a powerful tool for the elucidation of disease mechanisms and to provide new insights into the diagnosis, treatment, and prognosis of AN. 
  • 727
  • 17 Dec 2021
Topic Review
STAT3 Enhances Sensitivity of Glioblastoma to Cell Death
Glioblastoma is the most common primary brain cancer in adults. One reason for the development and malignancy of this tumor is the misregulation of certain cellular proteins. The oncoprotein Signal Transducer and Activator of Transcription (STAT3) that is frequently overactive in glioblastoma cells is associated with more aggressive disease and decreased patient survival. Autophagy is a form of cellular self digestion that normally maintains cell integrity and provides nutrients and basic building blocks required for growth. While glioblastoma is known to be particularly resistant to conventional therapies, recent research has suggested that these tumors are more sensitive to excessive overactivation of autophagy, leading to autophagy-dependent tumor cell death.
  • 727
  • 26 Jan 2022
Topic Review
Imaging Biomarkers for Neuroinflammation
Inflammation is one key process in driving cellular redox homeostasis toward oxidative stress, which perpetuates inflammation. In the brain, this interplay results in a vicious cycle of cell death, the loss of neurons, and leakage of the blood–brain barrier. Hence, the neuroinflammatory response fuels the development of acute and chronic inflammatory diseases. Interrogation of the interplay between inflammation, oxidative stress, and cell death in neurological tissue in vivo is very challenging. The complexity of the underlying biological process and the fragility of the brain limit our understanding of the cause and the adequate diagnostics of neuroinflammatory diseases. Notable redox biomarkers for imaging with positron emission tomography (PET) tracers are the 18 kDa translocator protein (TSPO) and monoamine oxygenase B (MAO–B).
  • 726
  • 20 May 2021
Topic Review
Animal Models for Human Neurodegenerative Diseases
Animal models of human neurodegenerative disease have been investigated for several decades. In recent years, zebrafish (Danio rerio) and medaka (Oryzias latipes) have become popular in pathogenic and therapeutic studies about human neurodegenerative diseases due to their small size, the optical clarity of embryos, their fast development, and their suitability to large-scale therapeutic screening. 
  • 726
  • 22 Oct 2021
Topic Review
Exosomes and Brain Metastases
Brain metastases (BM) are a frequent complication in patients with advanced stages of cancer, associated with impairment of the neurological function, quality of life, prognosis, and survival. BM treatment consists of a combination of the available cancer therapies, such as surgery, radiotherapy, chemotherapy, immunotherapy and targeted therapies. Even so, cancer patients with BM are still linked to poor prognosis, with overall survival being reported as 12 months or less. Intercellular communication has a pivotal role in the development of metastases, therefore, it has been extensively studied not only to better understand the metastization process, but also to further develop new therapeutic strategies. Exosomes have emerged as key players in intercellular communication being potential therapeutic targets, drug delivery systems (DDS) or biomarkers.
  • 726
  • 22 Oct 2021
Topic Review
Plant Lipid Metabolism Responses to Phosphate Scarcity
Low phosphate (Pi) availability in soils severely limits crop growth and production. Plants have evolved to have numerous physiological and molecular adaptive mechanisms to cope with Pi starvation. The release of Pi from membrane phospholipids is considered to improve plant phosphorus (P) utilization efficiency in response to Pi starvation and accompanies membrane lipid remodeling. Researchers summarize recent discoveries related to this topic and the molecular basis of membrane phospholipid alteration in response to Pi depletion in plants at different subcellular levels. These findings will help to further elucidate the molecular mechanisms underlying plant adaptation to Pi starvation and thus help to develop crop cultivars with high P utilization efficiency.
  • 726
  • 09 Sep 2022
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