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Topic Review
Amyloid Fragmentation and Disaggregation in Yeast and Animals
Amyloids are filamentous protein aggregates that are associated with a number of incurable diseases, termed amyloidoses. Amyloids can also manifest as infectious or heritable particles, known as prions. While just one prion is known in humans and animals, more than ten prion amyloids have been discovered in fungi. The propagation of fungal prion amyloids requires the chaperone Hsp104, though in excess it can eliminate some prions. Even though Hsp104 acts to disassemble prion fibrils, at normal levels it fragments them into multiple smaller pieces, which ensures prion propagation and accelerates prion conversion. Animals lack Hsp104, but disaggregation is performed by the same complement of chaperones that assist Hsp104 in yeast—Hsp40, Hsp70, and Hsp110. Exogenous Hsp104 can efficiently cooperate with these chaperones in animals and promotes disaggregation, especially of large amyloid aggregates, which indicates its potential as a treatment for amyloid diseases. However, despite the significant effects, Hsp104 and its potentiated variants may be insufficient to fully dissolve amyloid.
  • 712
  • 20 Jan 2022
Topic Review
Assessment of Blood Platelet Function
Platelets are non-nucleated components of blood. Their best recognized physiological function is primary hemostasis, i.e., formation of the hemostatic plug in the site of blood vessel injury. The plug not only limits blood extravasation, but it also creates a procoagulant surface on which the coagulation cascade develops to form fibrin mesh which stabilizes the plug. Effective formation of the hemostatic plug is assured by the ability of platelet to adhere to the site of injury and by firm binding to adjacent platelets. Such a profound phenotype switch from a circulating blood component to an element of a structure which withholds blood outflow demands significant alterations in platelet biochemistry. These alterations are generally termed platelet activation.
  • 711
  • 02 Feb 2021
Topic Review
Histone Post-Translational Modifications in a Mitotic Chromosome
During mitosis, many cellular structures are organized to segregate the replicated genome to the daughter cells. Chromatin is condensed to shape a mitotic chromosome. A multiprotein complex known as kinetochore is organized on a specific region of each chromosome, the centromere, which is defined by the presence of a histone H3 variant called CENP-A. The cytoskeleton is re-arranged to give rise to the mitotic spindle that binds to kinetochores and leads to the movement of chromosomes. How chromatin regulates different activities during mitosis is not well known. The role of histone post-translational modifications (HPTMs) in mitosis has been recently revealed. Specific HPTMs participate in local compaction during chromosome condensation. On the other hand, HPTMs are involved in CENP-A incorporation in the centromere region, an essential activity to maintain centromere identity. HPTMs also participate in the formation of regulatory protein complexes, such as the chromosomal passenger complex (CPC) and the spindle assembly checkpoint (SAC). 
  • 711
  • 31 Aug 2022
Topic Review
Sirtuin 6 in Metabolic Activity
Sirtuins, in mammals, are a group of seven enzymes (SIRT1–SIRT7) involved in the post-translational modification of proteins—they are considered longevity proteins. Sirtuin 6 (SIRT6), classified as class IV, is located on the cell nucleus. It affects many molecular pathways involved in aging: telomere maintenance, DNA repair, inflammatory processes or glycolysis. SIRT6 is involved in the regulation of homeostasis—an increase in the protein’s activity has been noted in calorie-restriction diets and with significant weight loss, among others. Expression of this protein is also elevated in people who regularly exercise. 
  • 711
  • 28 Aug 2023
Topic Review
Classification of Mechanoreceptors and Their Physiological Importance
Mechanosensitive ion channels comprise a broad group of proteins that sense mechanical extracellular and intracellular changes, translating them into cation influx to adapt and respond to these physical cues. All cells in the organism are mechanosensitive, and these physical cues have proven to have an important role in regulating proliferation, cell fate and differentiation, migration and cellular stress, among other processes. Indeed, the mechanical properties of the extracellular matrix in cancer change drastically due to high cell proliferation and modification of extracellular protein secretion, suggesting an important contribution to tumor cell regulation.
  • 711
  • 22 Sep 2023
Topic Review
ADAMTS and Fertility in Females and Males
The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) family genes code for key metalloproteinases in the remodeling process of different ECM. Several genes of this family encode for proteins with important functions in reproductive processes; in particular, ADAMTS1, 4, 5 and 9 are genes that are differentially expressed in cell types and the physiological stages of reproductive tissues. ADAMTS enzymes degrade proteoglycans in the ECM of the follicles so that the oocytes can be released and regulate follicle development during folliculogenesis, favoring the action of essential growth factors, such as FGF-2, FGF-7 and GDF-9. The transcriptional regulation of ADAMTS1 and 9 in preovulatory follicles occurs because of the gonadotropin surge in preovulatory follicles, via the progesterone/progesterone receptor complex. In addition, in the case of ADAMTS1, pathways involving protein kinase A (PKA), extracellular signal regulated protein kinase (ERK1/2) and the epidermal growth factor receptor (EGFR) might contribute to ECM regulation. Different Omic studies indicate the importance of genes of the ADAMTS family from a reproductive aspect. ADAMTS genes could serve as biomarkers for genetic improvement and contribute to enhance fertility and animal reproduction.
  • 710
  • 11 Aug 2023
Topic Review
RAC1 Activation in Metastatic Cutaneous Melanoma
Metastasis is a complex process by which cancer cells escape from the primary tumor to colonize distant organs. RAC1 is a member of the RHO family of small guanosine triphosphatases that plays an important role in cancer migration, invasion, angiogenesis and metastasis. 
  • 709
  • 27 Oct 2021
Topic Review
Molecularly Imprinted Polymer-Based Sensors for SARS-CoV-2
Since the first reported case of COVID-19 in 2019 in China and the official declaration from the World Health Organization in March 2021 as a pandemic, fast and accurate diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has played a major role worldwide. For this reason, various methods have been developed, comprising reverse transcriptase-polymerase chain reaction (RT-PCR), immunoassays, clustered regularly interspaced short palindromic repeats (CRISPR), reverse transcription loop-mediated isothermal amplification (RT-LAMP), and bio(mimetic)sensors. Among the developed methods, RT-PCR is so far the gold standard. IUPAC defines the term biomimetic as “Refers a laboratory procedure designed to imitate a natural chemical process. Also refers to a compound that mimics a biological material in structure or function“. The lotus effect at a water-repelling surface is the best-known example of biomimetic systems. One important motivation for the development and application of biomimetic recognition elements is their potentially higher stability and lower price as compared with biomolecules. 
  • 709
  • 19 May 2022
Topic Review
Mushroom-Derived Compounds Targeting Disrupted Metabolism in Cancer
Cancer is responsible for lifelong disability and decreased quality of life. Cancer cells undergo numerous changes in their metabolic pathways, involving energy and biosynthetic processes, so that they can proliferate. Hence, the metabolic pathways appear as interesting targets for a broad spectrum of therapeutic approaches. Mushrooms possess biological activities relevant to disease-fighting and to the prevention of cancer. They have a long-standing tradition of use in ethnomedicine and have been included as an adjunct therapy during and after oncological care. Mushroom-derived compounds have also been reported to target the key signature of cancer cells in in vitro and in vivo studies.
  • 709
  • 27 Feb 2023
Topic Review
MiRNAs in Developing Axons
During neuronal circuit formation, axons progressively develop into a presynaptic compartment aided by extracellular signals. Axons display a remarkably high degree of autonomy supported in part by a local translation machinery that permits the subcellular production of proteins required for their development. MicroRNAs (miRNAs) are critical regulators of this machinery, orchestrating the spatiotemporal regulation of local translation in response to cues. On one hand, a cue-induced relief of miRNA-mediated inhibition leads to bursts of protein translation, on the other hand, a cue-induced miRNA activation, results in reduced protein production. Overall, miRNAs are key elements of the local translation regulatory network controlling axon development.
  • 708
  • 01 Dec 2020
Topic Review
Polymeric Micelles in Cancer Immunotherapy
Cancer immunotherapies have generated some miracles in the clinic by orchestrating our immune system to combat cancer cells. However, the safety and efficacy concerns of the systemic delivery of these immunostimulatory agents has limited their application. Nanomedicine-based delivery strategies (e.g., liposomes, polymeric nanoparticles, silico, etc.) play an essential role in improving cancer immunotherapies, either by enhancing the anti-tumor immune response, or reducing their systemic adverse effects. The versatility of working with biocompatible polymers helps these polymeric nanoparticles stand out as a key carrier to improve bioavailability and achieve specific delivery at the site of action. 
  • 708
  • 11 May 2021
Topic Review
Role of microRNAs in Obesity-Related Kidney Disease
miRNAs are short non-coding, single stranded RNA molecules who have a critical role in the regulation of gene expression.
  • 708
  • 09 Nov 2021
Topic Review
Chemical Biology of Reactive Sulfur Species in Plants
Abiotic and biotic stresses negatively affect plant cellular and biological processes, limiting their growth and productivity. Plants respond to these environmental cues and biotrophic attackers by activating intricate metabolic-molecular signaling networks precisely and coordinately. One of the initial signaling networks activated is involved in the generation of reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS). RSS has been proclaimed to be inexorably interlinked with all life forms from its inception to the present day.
  • 708
  • 16 Jan 2023
Topic Review
Dynamic Metabolic Regulation in BC
Bladder cancer (BC) represents a clinical, social, and economic challenge due to tumor-intrinsic characteristics, limitations of diagnostic techniques and a lack of personalized treatments. In the last decade, the use of liquid biopsy has grown as a non-invasive approach to characterize tumors. Moreover, the emergence of omics has increased our knowledge of cancer biology and identified critical BC biomarkers. The rewiring between epigenetics and metabolism has been closely linked to tumor phenotype. Chromatin remodelers interact with each other to control gene silencing in BC, but also with stress-inducible factors or oncogenic signaling cascades to regulate metabolic reprogramming towards glycolysis, the pentose phosphate pathway, and lipogenesis. Concurrently, one-carbon metabolism supplies methyl groups to histone and DNA methyltransferases, leading to the hypermethylation and silencing of suppressor genes in BC. Conversely, α-KG and acetyl-CoA enhance the activity of histone demethylases and acetyl transferases, increasing gene expression, while succinate and fumarate have an inhibitory role. 
  • 707
  • 24 Jun 2021
Topic Review
Co-Translational Quality Control Induced by Translational Arrest
Genetic mutations, mRNA processing errors, and lack of availability of charged tRNAs sometimes slow down or completely stall translating ribosomes. Since an incomplete nascent chain derived from stalled ribosomes may function anomalously, such as by forming toxic aggregates, surveillance systems monitor every step of translation and dispose of such products to prevent their accumulation. Yeast models with powerful genetics and biochemical techniques have contributed to uncovering the mechanism of the co-translational quality control system, which eliminates the harmful products generated from aberrant translation. 
  • 707
  • 22 Feb 2023
Topic Review
Site-Search Process for Synaptic Protein-DNA Complexes
The assembly of synaptic protein-DNA complexes by specialized proteins is critical for bringing together two distant sites within a DNA molecule or bridging two DNA molecules. The assembly of such synaptosomes is needed in numerous genetic processes requiring the interactions of two or more sites. The molecular mechanisms by which proteins bring the sites together, enabling the assembly of synaptosomes, remain unknown. Such proteins can utilize sliding, jumping, and segmental transfer pathways for the single-site search process, but none of these pathways explains how the synaptosome assembles. Here we used restriction enzyme SfiI, that requires the assembly of synaptosome for DNA cleavage, as our experimental system and applied time-lapse high-speed AFM (HS-AFM) to directly visualize the site search process accomplished by the SfiI enzyme.
  • 706
  • 17 Jan 2022
Topic Review
Carbapenem-Resistant Klebsiella pneumoniae
Klebsiella pneumoniae is a Gram-negative opportunistic pathogen responsible for a variety of community and hospital infections. Infections caused by carbapenem-resistant K. pneumoniae (CRKP) constitute a major threat for public health and are strongly associated with high rates of mortality, especially in immunocompromised and critically ill patients. Adhesive fimbriae, capsule, lipopolysaccharide (LPS), and siderophores or iron carriers constitute the main virulence factors which contribute to the pathogenicity of K. pneumoniae.
  • 706
  • 31 Jan 2023
Topic Review
Gut Microbiota in Breast Cancer and Drug Resistance
Breast cancer is the most common malignancy in women worldwide. The cause of cancer is multifactorial. An early diagnosis and the appropriate treatment of cancer can improve the chances of survival. Recent studies have shown that breast cancer is influenced by the microbiota. Different microbial signatures have been identified in the breast microbiota, which have different patterns depending on the stage and biological subgroups. The human digestive system contains approximately 100 trillion bacteria. The gut microbiota is an emerging field of research that is associated with specific biological processes in many diseases, including cardiovascular disease, obesity, diabetes, brain disease, rheumatoid arthritis, and cancer.
  • 706
  • 03 Apr 2023
Topic Review
Microsampling Applications Monitoring Lipids and Metabolites
Due to its numerous advantages, microsampling technology has become widely utilized in blood collection and storage across various fields. There has been a notable increase in studies combining microsampling with mass spectrometry techniques, with mass spectrometry being the preferred analytical tool for measuring lipids and metabolites. The synergy of microsampling with mass spectrometry brings forth several benefits, including minimal sample requirements, the ability to analyze multiple analytes simultaneously, and high sensitivity and specificity. Microsampling can be carried out by the patient without requiring trained personnel. This feature simplifies remote sampling, enhancing accessibility for individuals in remote areas and eliminating unnecessary, and in some cases, risky hospital visits for elderly individuals. 
  • 706
  • 23 Jan 2024
Topic Review
Actions of Insulin Expressed in the CNS
The expression of insulin receptors (IR) in the central nervous system (CNS) was first documented almost half a century ago. It is now known that both short (IR-A) and long (IR-B) isoform of this receptor is expressed in the hypothalamus, hippocampus, cerebral cortex, and cerebellum, the brain regions also associated with the production of insulin. In regard to the IR expression at the cellular level, it was shown that, unlike neurons that only express IR-A, astrocytes express both IR-A and IR-B. Ever since the transport of insulin across the BBB and the expression of functional IR in the CNS was documented, attempts have been made to learn more about the effects of insulin on the brain. In line with that, numerous actions of insulin in the CNS have been described so far. It has been known that insulin takes part in controlling food intake and body weight. In addition to that, insulin actions are also essential for proper neuronal development and survival, cognition, brain cholesterol synthesis, hepatic glucose production, lipolysis and lipogenesis, and even reproductive competence. Moreover, it was also shown that impairment in insulin signaling could trigger depression- and anxiety-like behaviors. Although new roles of insulin keep emerging, it is still mainly unknown which of them can be attributed to brain-derived and which to pancreatic insulin, or whether their actions in the CNS overlap and to what extent.
  • 705
  • 12 Apr 2023
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