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Topic Review
Histone Genes in Drosophila
The evolution of the GC (guanine cytosine) content at the third codon position of the histone genes (H1, H2A, H2B, H3, H4, H2AvD, H3.3A, H3.3B, and H4r) in 12 or more Drosophila species is reviewed. For explaining the evolution of the GC content at the third codon position of the genes, a model assuming selection with a deleterious effect for adenine/thymine and a size effect is presented. The applicability of the model to whole-genome genes is also discussed. 
  • 570
  • 27 May 2021
Topic Review
Hyperprogressive Disease
Hyperprogressive disease (HPD) is an adverse outcome of immunotherapy consisting in an acceleration of tumor growth, often accompanied by prompt clinical deterioration.
  • 458
  • 27 May 2021
Topic Review
TRPC Channels
Transient receptor potential canonical (TRPC) channels are ubiquitously expressed in excitable and non-excitable cardiac cells where they sense and respond to a wide variety of physical and chemical stimuli. As other TRP channels, TRPC channels may form homo or heterotetrameric ion channels, and they can associate with other membrane receptors and ion channels to regulate intracellular calcium concentration. Dysfunctions of TRPC channels are involved in many types of cardiovascular diseases. Significant increase in the expression of different TRPC isoforms was observed in different animal models of heart infarcts and in vitro experimental models of ischemia and reperfusion. TRPC channel-mediated increase of the intracellular Ca2+ concentration seems to be required for the activation of the signaling pathway that plays minor roles in the healthy heart, but they are more relevant for cardiac responses to ischemia, such as the activation of different factors of transcription and cardiac hypertrophy, fibrosis, and angiogenesis.
  • 682
  • 26 May 2021
Topic Review
Sulfate Reduction in Intestinal Bacteria
Sulfate is present in foods, beverages, and drinking water. Its reduction and concentration in the gut depend on the intestinal microbiome activity, especially sulfate-reducing bacteria (SRB), which can be involved in inflammatory bowel disease (IBD). Assimilatory sulfate reduction (ASR) is present in all living organisms. In this process, sulfate is reduced to hydrogen sulfide and then included in cysteine and methionine biosynthesis. In contrast to assimilatory sulfate reduction, the dissimilatory process is typical for SRB. A terminal product of this metabolism pathway is hydrogen sulfide, which can be involved in gut inflammation and also causes problems in industries (due to corrosion effects).
  • 984
  • 26 May 2021
Topic Review
ER Stress Responses
The endoplasmic reticulum (ER) is a critical organelle, storing the majority of calcium and governing protein translation. Thus, it is crucial to keep the homeostasis in all ER components and machineries. The ER stress sensor pathways, including IRE1/sXBP1, PERK/EIf2α and ATF6, orchestrate the major regulatory circuits to ensure ER homeostasis. The embryonic or postnatal lethality that occurs upon genetic depletion of these sensors reveals the essential role of the ER stress pathway in cell biology. In contrast, the impairment or excessive activation of ER stress has been reported to cause or aggravate several diseases such as atherosclerosis, diabetes, NAFDL/NASH, obesity and cancer. Being part of innate immunity, myeloid cells are the first immune cells entering the inflammation site. Upon entry into a metabolically stressed disease environment, activation of ER stress occurs within the myeloid compartment, leading to the modulation of their phenotype and functions.
  • 424
  • 26 May 2021
Topic Review
Stem Cell-Derived Extracellular Vesicles
Extracellular vesicles (EVs), which are the main paracrine components of stem cells, mimic the regenerative capacity of these cells. Stem cell-derived EVs (SC-EVs) have been used for the treatment of various forms of tissue injury in preclinical trials through maintenance of their stemness, induction of regenerative phenotypes, apoptosis inhibition, and immune regulation. The efficiency of SC-EVs may be enhanced by selecting the appropriate EV-producing cells and cell phenotypes, optimizing cell culture conditions for the production of optimal EVs, and further engineering the EVs produced to transport therapeutic and targeting molecules.
  • 722
  • 26 May 2021
Topic Review
Angiogenic Properties of Placenta-Derived EVs
Angiogenesis is one of the main processes that coordinate the biological events leading to a successful pregnancy, and its imbalance characterizes several pregnancy-related diseases, including preeclampsia. Intracellular interactions via extracellular vesicles (EVs) contribute to pregnancy’s physiology and pathophysiology, and to the fetal–maternal interaction.
  • 458
  • 26 May 2021
Topic Review
Homologous Recombination Repair Deficiency
Homologous recombination repair deficiency (HRD) can be observed in virtually all cancer types. Cells possess a complex set of non-redundant and partially overlapping pathways to detect and repair DNA damage. In cancer, DNA damage repair (DDR) is frequently disrupted, leading to genomic instability. One of the pathways that is regularly altered in cancer is HR. HR is an important pathway for the repair of double-strand DNA breaks (DSBs) during the S and G2 phase of the cell cycle, i.e., after DNA replication has occurred. HR is considered a relatively error-free process because it uses an intact sister chromatid to guide DNA repair. HR deficiency (HRD) leads to enhanced reliance on alternative pathways involved in DSB repair, i.e., classical NHEJ, alternative end joining, and single-strand annealing. These pathways repair DSBs without a homologous DNA template, resulting in characteristic genomic scars across the genome.
  • 797
  • 25 May 2021
Topic Review
AP-1 Transcription Factors in Myeloma
Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the clonal expansion of malignant plasma cells within the bone marrow. Activator Protein-1 (AP-1) transcription factors (TFs), comprised of the JUN, FOS, ATF and MAF multigene families, are implicated in a plethora of physiologic processes and tumorigenesis including plasma cell differentiation and MM pathogenesis. Depending on the genetic background, the tumor stage, and cues of the tumor microenvironment, specific dimeric AP-1 complexes are formed. For example, AP-1 complexes containing Fra-1, Fra-2 and B-ATF play central roles in the transcriptional control of B cell development and plasma cell differentiation, while dysregulation of AP-1 family members c-Maf, c-Jun, and JunB is associated with MM cell proliferation, survival, drug resistance, bone marrow angiogenesis, and bone disease. The present review article summarizes our up-to-date knowledge on the role of AP-1 family members in plasma cell differentiation and MM pathophysiology. Moreover, it discusses novel, rationally derived approaches to therapeutically target AP-1 TFs, including protein-protein and protein-DNA binding inhibitors, epigenetic modifiers and natural products.
  • 1.6K
  • 25 May 2021
Topic Review
Hematopoietic Stem Cells
Hematopoietic cells consist of a heterogenous group of cells originating from hematopoietic stem cells (HSCs). HSCs differentiate into multi-potent progenitor cells (MPPs) which further produce circulating and tissue-residing blood cells of specific lineage. The bone marrow (BM) is the main hematopoietic organ in an adult and houses millions of immature and mature hematopoietic cells. HSCs reside as a rare cell population in the BM where they are maintained in quiescence as a reserve pool for hematopoiesis. When hematopoiesis is compromised, HSCs self-renew, proliferate and differentiate to replenish hematopoietic cells. As with all cells in an organism, hematopoietic cells utilize adenosine triphosphate (ATP) as a common energy currency. While it is fundamentally known that ATP is produced anaerobically through glycolysis and aerobically through mitochondrial oxidative phosphorylation (OXPHOS), the contribution of these processes for energy production varies between hematopoietic cell type. While the BM microenvironment is predominantly hypoxic, different hematopoietic cells utilize both glycolysis and OXPHOS at varying degrees for survival.
  • 772
  • 25 May 2021
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