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Frontiers in Biology

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https://www.readbyqxmd.com/read/29527223/pten-at-the-interface-of-immune-tolerance-and-tumor-suppression
#1
Andrew Brandmaier, Sheng-Qi Hou, Sandra Demaria, Silvia C Formenti, Wen H Shen
BACKGROUND: PTEN is well known to function as a tumor suppressor that antagonizes oncogenic signaling and maintains genomic stability. The PTEN gene is frequently deleted or mutated in human cancers and the wide cancer spectrum associated with PTEN deficiency has been recapitulated in a variety of mouse models of Pten deletion or mutation. Pten mutations are highly penetrant in causing various types of spontaneous tumors that often exhibit resistance to anticancer therapies including immunotherapy...
June 2017: Frontiers in Biology
https://www.readbyqxmd.com/read/28473847/the-radial-organization-of-neuronal-primary-cilia-is-acutely-disrupted-by-seizure-and-ischemic-brain-injury
#2
Gregory W Kirschen, Hanxiao Liu, Tracy Lang, Xuelin Liang, Shaoyu Ge, Qiaojie Xiong
BACKGROUND: Neuronal primary cilia are sensory organelles that are critically involved in the proper growth, development, and function of the central nervous system (CNS). Recent work also suggests that they signal in the context of CNS injury, and that abnormal ciliary signaling may be implicated in neurological diseases. METHODS: We quantified the distribution of neuronal primary cilia alignment throughout the normal adult mouse brain by immunohistochemical staining for the primary cilia marker adenylyl cyclase III (ACIII) and measuring the angles of primary cilia with respect to global and local coordinate planes...
April 2017: Frontiers in Biology
https://www.readbyqxmd.com/read/28580010/molecular-and-genetic-insights-into-an-infantile-epileptic-encephalopathy-cdkl5-disorder
#3
Ailing Zhou, Song Han, Zhaolan Joe Zhou
BACKGROUND: The discovery that mutations in cyclin-dependent kinase-like 5 (CDKL5) gene are associated with infantile epileptic encephalopathy has stimulated world-wide research effort to understand the molecular and genetic basis of CDKL5 disorder. Given the large number of literature published thus far, this review aims to summarize current genetic studies, draw a consensus on proposed molecular functions, and point to gaps of knowledge in CDKL5 research. METHODS: A systematic review process was conducted using the PubMed search engine focusing on CDKL5 studies in the recent ten years...
February 2017: Frontiers in Biology
https://www.readbyqxmd.com/read/29033980/cellular-physiological-and-pathological-aspects-of-the-long-non-coding-rna-neat1
#4
Pang-Kuo Lo, Benjamin Wolfson, Qun Zhou
BACKGROUND: The majority of mammalian genomes have been found to be transcribed into non-coding RNAs. One category of non-coding RNAs is classified as long non-coding RNAs (lncRNAs) based on their transcript sizes larger than 200 nucleotides. Growing evidence has shown that lncRNAs are not junk transcripts and play regulatory roles in multiple aspects of biological processes. Dysregulation of lncRNA expression has also been linked to diseases, in particular cancer. Therefore, studies of lncRNAs have attracted significant interest in the field of medical research...
December 2016: Frontiers in Biology
https://www.readbyqxmd.com/read/28133476/neuronal-activity-controls-the-development-of-interneurons-in-the-somatosensory-cortex
#5
Rachel Babij, Natalia De Marco Garcia
BACKGROUND: Neuronal activity in cortical areas regulates neurodevelopment by interacting with defined genetic programs to shape the mature central nervous system. Electrical activity is conveyed to sensory cortical areas via intracortical and thalamocortical neurons, and includes oscillatory patterns that have been measured across cortical regions. OBJECTIVE: In this work, we review the most recent findings about how electrical activity shapes the developmental assembly of functional circuitry in the somatosensory cortex, with an emphasis on interneuron maturation and integration...
December 2016: Frontiers in Biology
https://www.readbyqxmd.com/read/28974957/phosphodiesterase-4-inhibitors-and-drugs-of-abuse-current-knowledge-and-therapeutic-opportunities
#6
Christopher M Olsen, Qing-Song Liu
BACKGROUND: Long-term exposure to drugs of abuse causes an up-regulation of the cAMP-signaling pathway in the nucleus accumbens and other forebrain regions, this common neuroadaptation is thought to underlie aspects of drug tolerance and dependence. Phosphodiesterase 4 (PDE4) is an enzyme that the selective hydrolyzes intracellular cAMP. It is expressed in several brain regions that regulate the reinforcing effects of drugs of abuse. OBJECTIVE: Here, we review the current knowledge about central nervous system (CNS) distribution of PDE4 isoforms and the effects of systemic and brain-region specific inhibition of PDE4 on behavioral models of drug addiction...
October 2016: Frontiers in Biology
https://www.readbyqxmd.com/read/27956894/modeling-axonal-defects-in-hereditary-spastic-paraplegia-with-human-pluripotent-stem-cells
#7
Kyle R Denton, Chongchong Xu, Harsh Shah, Xue-Jun Li
BACKGROUND: Cortical motor neurons, also known as upper motor neurons, are large projection neurons whose axons convey signals to lower motor neurons to control the muscle movements. Degeneration of cortical motor neuron axons is implicated in several debilitating disorders, including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis (ALS). Since the discovery of the first HSP gene, SPAST that encodes spastin, over 70 distinct genetic loci associated with HSP have been identified...
October 2016: Frontiers in Biology
https://www.readbyqxmd.com/read/28367160/neural-stem-cell-heterogeneity-through-time-and-space-in-the-ventricular-subventricular-zone
#8
Gabrielle Rushing, Rebecca A Ihrie
BACKGROUND: The origin and classification of neural stem cells (NSCs) has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expression have established that these cells are a heterogeneous pool in both the embryonic and adult brain. The discovery and additional characterization of adult NSCs has introduced the possibility of using these cells as a source for neuronal and glial replacement following injury or disease...
August 2016: Frontiers in Biology
https://www.readbyqxmd.com/read/28261266/locus-and-cell-type-specific-epigenetic-switching-during-cellular-differentiation-in-mammals
#9
Ying-Tao Zhao, Maria Fasolino, Zhaolan Zhou
BACKGROUND: Epigenomic reconfiguration, including changes in DNA methylation and histone modifications, is crucial for the differentiation of embryonic stem cells (ESCs) into somatic cells. However, the extent to which the epigenome is reconfigured and the interplay between components of the epigenome during cellular differentiation remain poorly defined. METHODS: We systematically analyzed and compared DNA methylation, various histone modification, and transcriptome profiles in ESCs with those of two distinct types of somatic cells from human and mouse...
August 2016: Frontiers in Biology
https://www.readbyqxmd.com/read/28261265/new-insights-into-transcriptional-and-leukemogenic-mechanisms-of-aml1-eto-and-e2a-fusion-proteins
#10
Jian Li, Chun Guo, Nickolas Steinauer, Jinsong Zhang
BACKGROUND: Nearly 15% of acute myeloid leukemia (AML) cases are caused by aberrant expression of AML1-ETO, a fusion protein generated by the t(8;21) chromosomal translocation. Since its discovery, AML1-ETO has served as a prototype to understand how leukemia fusion proteins deregulate transcription to promote leukemogenesis. Another leukemia fusion protein, E2A-Pbx1, generated by the t(1;19) translocation, is involved in acute lymphoblastic leukemias (ALLs). While AML1-ETO and E2A-Pbx1 are structurally unrelated fusion proteins, we have recently shown that a common axis, the ETO/E-protein interaction, is involved in the regulation of both fusion proteins, underscoring the importance of studying protein-protein interactions in elucidating the mechanisms of leukemia fusion proteins...
August 2016: Frontiers in Biology
https://www.readbyqxmd.com/read/28473846/transgenic-mouse-models-for-studying-adult-neurogenesis
#11
Fatih Semerci, Mirjana Maletic-Savatic
The mammalian hippocampus shows a remarkable capacity for continued neurogenesis throughout life. Newborn neurons, generated by the radial neural stem cells (NSCs), are important for learning and memory as well as mood control. During aging, the number and responses of NSCs to neurogenic stimuli diminish, leading to decreased neurogenesis and age-associated cognitive decline and psychiatric disorders. Thus, adult hippocampal neurogenesis has garnered significant interest because targeting it could be a novel potential therapeutic strategy for these disorders...
June 2016: Frontiers in Biology
https://www.readbyqxmd.com/read/26973699/smoothened-regulation-in-response-to-hedgehog-stimulation
#12
Kai Jiang, Jianhang Jia
The Hedgehog (Hh) signaling pathway play critical roles in embryonic development and adult tissue homeostasis. A critical step in Hh signal transduction is how Hh receptor Patched (Ptc) inhibits the atypical G protein-coupled receptor Smoothened (Smo) in the absence of Hh and how this inhibition is release by Hh stimulation. It is unlikely that Ptc inhibits Smo by direct interaction. Here we discuss how Hh regulates the phosphorylation and ubiquitination of Smo, leading to cell surface and ciliary accumulation of Smo in Drosophila and vertebrate cells, respectively...
December 1, 2015: Frontiers in Biology
https://www.readbyqxmd.com/read/26913049/functional-states-of-resident-vascular-stem-cells-and-vascular-remodeling
#13
Desiree F Leach, Mitzi Nagarkatti, Prakash Nagarkatti, Taixing Cui
Recent evidence indicates that different types of vascular stem cells (VSCs) reside within the mural layers of arteries and veins. The precise identities of these resident VSCs are still unclear; generally, postnatal vasculature contains multilineage stem cells and vascular cell lineage-specific progenitor/stem cells which may participate in both vascular repair and lesion formation. However, the underlying mechanism remains poorly understood. In this review, we summarize the potential molecular mechanisms, which may control the quiescence and activation of resident VSCs and highlight a notion that the differential states of resident VSCs are directly linked to vascular repair or lesion formation...
October 1, 2015: Frontiers in Biology
https://www.readbyqxmd.com/read/26692106/beclin-1-vps34-complex-architecture-understanding-the-nuts-and-bolts-of-therapeutic-targets
#14
Deanna H Morris, Calvin K Yip, Yi Shi, Brian T Chait, Qing Jun Wang
Autophagy is an important lysosomal degradation pathway that aids in the maintenance of cellular homeostasis by breaking down and recycling intracellular contents. Dysregulation of autophagy is linked to a growing number of human diseases. The Beclin 1-Vps34 protein-protein interaction network is critical for autophagy regulation and is therefore essential to cellular integrity. Manipulation of autophagy, in particular via modulation of the action of the Beclin 1-Vps34 complexes, is considered a promising route to combat autophagy-related diseases...
October 2015: Frontiers in Biology
https://www.readbyqxmd.com/read/27683589/less-is-more-nutrient-limitation-induces-cross-talk-of-nutrient-sensing-pathways-with-nad-homeostasis-and-contributes-to-longevity
#15
Felicia Tsang, Su-Ju Lin
Nutrient sensing pathways and their regulation grant cells control over their metabolism and growth in response to changing nutrients. Factors that regulate nutrient sensing can also modulate longevity. Reduced activity of nutrient sensing pathways such as glucose-sensing PKA, nitrogen-sensing TOR and S6 kinase homolog Sch9 have been linked to increased life span in the yeast, Saccharomyces cerevisiae, and higher eukaryotes. Recently, reduced activity of amino acid sensing SPS pathway was also shown to increase yeast life span...
August 2015: Frontiers in Biology
https://www.readbyqxmd.com/read/28280503/new-therapeutic-strategies-targeting-d1-type-dopamine-receptors-for-neuropsychiatric-disease
#16
Young-Cho Kim, Stephanie L Alberico, Eric Emmons, Nandakumar S Narayanan
The neurotransmitter dopamine acts via two major classes of receptors, D1-type and D2-type. D1 receptors are highly expressed in the striatum and can also be found in the cerebral cortex. Here we review the role of D1 dopamine signaling in two major domains: L-DOPA-induced dyskinesias in Parkinson's disease and cognition in neuropsychiatric disorders. While there are many drugs targeting D2-type receptors, there are no drugs that specifically target D1 receptors. It has been difficult to use selective D1-receptor agonists for clinical applications due to issues with bioavailability, binding affinity, pharmacological kinetics, and side effects...
June 2015: Frontiers in Biology
https://www.readbyqxmd.com/read/26557138/the-bacterial-and-host-factors-associated-with-extrapulmonary-dissemination-of-mycobacterium-tuberculosis
#17
Dong Yang, Ying Kong
With high morbidity and mortality worldwide, tuberculosis (TB) is still an important public health threat. The majority of human TB cases are caused by Mycobacterium tuberculosis. Although pulmonary TB is the most common presentation, M. tuberculosis can disseminate into other organs and causes extrapulmonary TB (EPTB). The dissemination of bacteria from the initial site of infection to other organs can lead to fatal diseases, such as miliary and meningeal TB. Thoroughly understanding the mechanisms and pathways of dissemination would develop therapies to prevent the lethal prognosis of EPTB (miliary and meningeal TB) and vaccines to promote the development of adaptive immunity...
June 2015: Frontiers in Biology
https://www.readbyqxmd.com/read/26494984/role-of-upstream-stimulatory-factor-2-in-diabetic-nephropathy
#18
Shuxia Wang
Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD). About 20%-30% of people with type 1 and type 2 diabetes develop DN. DN is characterized by both glomerulosclerosis with thickening of the glomerular basement membrane and mesangial matrix expansion, and tubulointerstitial fibrosis. Hyperglycemia and the activation of the intra-renal renin-angiotensin system (RAS) in diabetes have been suggested to play a critical role in the pathogenesis of DN. However, the mechanisms are not well known...
June 2015: Frontiers in Biology
https://www.readbyqxmd.com/read/26366162/regulation-of-hedgehog-signaling-by-ubiquitination
#19
Elaine Y C Hsia, Yirui Gui, Xiaoyan Zheng
The Hedgehog (Hh) signaling pathway plays crucial roles both in embryonic development and in adult stem cell function. The timing, duration and location of Hh signaling activity need to be tightly controlled. Abnormalities of Hh signal transduction lead to birth defects or malignant tumors. Recent data point to ubiquitination-related posttranslational modifications of several key Hh pathway components as an important mechanism of regulation of the Hh pathway. Here we review how ubiquitination regulates the localization, stability and activity of the key Hh signaling components...
June 2015: Frontiers in Biology
https://www.readbyqxmd.com/read/29750082/high-on-food-the-interaction-between-the-neural-circuits-for-feeding-and-for-reward
#20
Jing-Jing Liu, Diptendu Mukherjee, Doron Haritan, Bogna Ignatowska-Jankowska, Ji Liu, Ami Citri, Zhiping P Pang
Hunger, mostly initiated by a deficiency in energy, induces food seeking and intake. However, the drive toward food is not only regulated by physiological needs, but is motivated by the pleasure derived from ingestion of food, in particular palatable foods. Therefore, feeding is viewed as an adaptive motivated behavior that involves integrated communication between homeostatic feeding circuits and reward circuits. The initiation and termination of a feeding episode are instructed by a variety of neuronal signals, and maladaptive plasticity in almost any component of the network may lead to the development of pathological eating disorders...
April 2015: Frontiers in Biology
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