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Topic Review
ARHGAP11B
ARHGAP11B is a human-specific gene that likely played a crucial role in human neocortex evolution by inducing hallmarks of cortical expansion. In contrast to its ancestral paralog, ARHGAP11A, ARHGAP11B does not act as a Rho GTPase Activating Protein in the nucleus but is localized in mitochondria and increases glutaminolysis. This increase is a prerequisite for increased basal progenitor proliferation – one essential basis for cortical expansion.
  • 608
  • 28 May 2021
Topic Review
Calcium Sources to Somatic Release of Serotonin
The soma, dendrites and axon of neurons may display calcium-dependent release of transmitters and peptides. Such release is named extrasynaptic for occurring in absence of synaptic structures. Emphasis is given to the somatic release of serotonin by the classical leech Retzius neuron, which has allowed detailed studies on the fine steps from excitation to exocytosis. Trains of action potentials induce transmembrane calcium entry through L-type channels. For action potential frequencies above 5 Hz, summation of calcium transients on individual action potentials activates the second calcium source: ryanodine receptors produce calcium-induced calcium release. The resulting calcium tsunami activates mitochondrial ATP synthesis to fuel transport of vesicles to the plasma membrane. Serotonin that is released maintains a large-scale exocytosis by activating the third calcium source: serotonin autoreceptors coupled to phospholipase C promote IP3 production. Activated IP3 receptors in peripheral endoplasmic reticulum release calcium that promotes vesicle fusion. The Swiss-clock workings of the machinery for somatic exocytosis has a striking disadvantage. The essential calcium-releasing endoplasmic reticulum near the plasma membrane hinders the vesicle transport, drastically reducing the thermodynamic efficiency of the ATP expenses and elevating the energy cost of release. 
  • 608
  • 09 Feb 2022
Topic Review
Flipons and Condensates Enhances Evolution
A number of insights derive from viewing flipons as scaffolds for condensates. Flipons provide a controlled way to initiate condensate formation, one subject to natural selection. The alternative conformation localizes required factors needed to regulate transcription, RNA processing, and epigenetic modification, while excluding nucleosomes and other B-DNA- and A-RNA-specific proteins that produce competing outcomes.
  • 608
  • 22 Sep 2021
Topic Review
Schlafens in Cancer Cell Biology
Schlafens (SLFN) are a family of genes widely expressed in mammals, including humans and rodents. These intriguing proteins play different roles in regulating cell proliferation, cell differentiation, immune cell growth and maturation, and inhibiting viral replication. The emerging evidence is implicating Schlafens in cancer biology and chemosensitivity. Although Schlafens share common domains and a high degree of homology, different Schlafens act differently. In particular, they show specific and occasionally opposing effects in some cancer types. 
  • 608
  • 16 Sep 2021
Topic Review
cGAS–Sting Signaling in Alzheimer’s Disease
There is mounting evidence that the development of Alzheimer’s disease (AD) interacts extensively with immunological processes in the brain and extends beyond the neuronal compartment. Accumulation of misfolded proteins can activate an innate immune response that releases inflammatory mediators and increases the severity and course of the disease. It is widely known that type-I interferon-driven neuroinflammation in the central nervous system (CNS) accelerates the development of numerous acute and chronic CNS diseases. It is becoming better understood how the cyclic GMP–AMP synthase (cGAS) and its adaptor protein Stimulator of Interferon Genes (STING) triggers type-I IFN-mediated neuroinflammation.
  • 608
  • 10 May 2023
Topic Review
Read
In DNA sequencing, a read is an inferred sequence of base pairs (or base pair probabilities) corresponding to all or part of a single DNA fragment. A typical sequencing experiment involves fragmentation of the genome into millions of molecules, which are size-selected and ligated to adapters. The set of fragments is referred to as a sequencing library, which is sequenced to produce a set of reads.
  • 607
  • 24 Nov 2022
Topic Review
PPARs in Cancer Stromal Cells
Most anticancer therapies target malignant cancer cells while largely ignoring the surrounding noncancer cell components of the tumor or TME. The TME or tumor stroma comprises nonmalignant host cellular and acellular components, including, but not limited to, fibroblasts, immune cells, endothelial cells, fat cells, and noncellular components of the tumor niche such as the basement membrane and ECM. Although most normal host cells in the stroma possess certain tumor-suppressing abilities, the stroma will change during malignancy, causing the tumor stromal cells to confer pro- or anti-tumor properties in a context- and cell type-dependent manner. Over the past decades, the role of the TME in determining every aspect of cancer progression and the efficacy of treatment has become evident. The functions of PPARs in these stromal cells are increasingly appreciated and have direct or indirect impacts on cancer progression.
  • 606
  • 03 Jun 2021
Topic Review
Diffuse Large B-Cell Lymphomas
Diffuse large B-cell lymphoma (DLBCL) is the commonest form of lymphoid malignancy, with a prevalence of about 40% worldwide. The term DLBCL reflects the growth pattern and size of the neoplastic cells, which tend to diffusely efface the normal structure of the involved organ (most frequently the lymph node) and are provided with a diameter at least twice that of normal lymphocytes. Although during the last few years several distinct clinical-pathological categories of DLBCL have been reported in the literature, which are nowadays listed in the Revised 4th Edition of the WHO Classification of the Tumours of Haematopoietic and Lymphoid Tissues, about 80% of DLBCLs do not enter into any of these categories and are therefore termed not otherwise specified (NOS). DLBCL-NOS displays a quite variable morphology and only rarely consists of only one cytotype (centroblastic, immunoblastic or anaplastic). Thus, microscopic examination fails to define the cell of origin, prognostic indicators and novel potential therapeutic targets. The standard of care  is the immuno-chemotherapy R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), which cures up to 65% of patients. The remaining individuals with DLBCL-NOS experience resistant or relapsing disease and eventually die of it. This situation has promoted a huge number of studies focusing on the pathobiology of the tumour and based on high-throughput techniques, including gene expression profiling and next generation sequencing. In addition, attention has been focused on the mcroenvironmental composition, which can influence the behaviour and response to therapy of the tumour in conjunction with the molecular characteristics of neoplastic cells. The aim of the present review is to discuss the most recent acquisitions in the field of DLBCL-NOS based on the extensive application of molecular techniques, which paves the way to a more rational classification of the tumour along with the identification of effective prognostic indicators and novel therapeutic targets for  ad hoc personalised approaches. 
  • 606
  • 23 Jun 2021
Topic Review
Bromodomain Proteins in Cancer
This review provides an in depth analysis of the role of bromodomain-containing proteins in cancer development. As readers of acetylated lysine on nucleosomal histones, bromodomain proteins are poised to activate gene expression, and often promote cancer progression. We examined changes in gene expression patterns that are observed in bromodomain-containing proteins and associated with specific cancer types. We also mapped the protein–protein interaction network for the human bromodomain-containing proteins, discuss the cellular roles of these epigenetic regulators as part of nine different functional groups, and identify bromodomain-specific mechanisms in cancer development. Lastly, we summarize emerging strategies to target bromodomain proteins in cancer therapy, including those that may be essential for overcoming resistance. Overall, this review provides a timely discussion of the different mechanisms of bromodomain-containing proteins in cancer, and an updated assessment of their utility as a therapeutic target for a variety of cancer subtypes.
  • 606
  • 07 Aug 2021
Topic Review
Adiponectin System (Rescue Hormone)
The adipose tissue, regardless of its role in generating and storing energy, acts as a key player as an endocrine tissue, producing a wide scale of cytokines/hormones called adipokines. Adipokines such as leptin, resistin, visfatin and osteopontin own pro-inflammatory effects on the cardiovascular system in some cases. In contrast, some adipokines have cardioprotective and anti-inflammatory impacts including adiponectin, omentin, and apelin.
  • 606
  • 12 Jul 2022
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