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Frontiers in Biology

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https://www.readbyqxmd.com/read/28473847/the-radial-organization-of-neuronal-primary-cilia-is-acutely-disrupted-by-seizure-and-ischemic-brain-injury
#1
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/28133476/neuronal-activity-controls-the-development-of-interneurons-in-the-somatosensory-cortex
#2
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/27956894/modeling-axonal-defects-in-hereditary-spastic-paraplegia-with-human-pluripotent-stem-cells
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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/26989402/emerging-roles-of-autophagy-in-metabolism-and-metabolic-disorders
#16
Altea Rocchi, Congcong He
The global prevalence of metabolic disorders is an immediate threat to human health. Genetic features, environmental aspects and lifestyle changes are the major risk factors determining metabolic dysfunction in the body. Autophagy is a housekeeping stress-induced lysosomal degradation pathway, which recycles macromolecules and metabolites for new protein synthesis and energy production and regulates cellular homeostasis by clearance of damaged protein or organelles. Recently, a dramatically increasing number of literatures has shown that defects of the autophagic machinery is associated with dysfunction of multiple metabolic tissues including pancreatic β cells, liver, adipose tissue and muscle, and is implicated in metabolic disorders such as obesity and insulin resistance...
April 2015: Frontiers in Biology
https://www.readbyqxmd.com/read/26213533/analytical-strategies-for-studying-stem-cell-metabolism
#17
James M Arnold, William T Choi, Arun Sreekumar, Mirjana Maletić-Savatić
Owing to their capacity for self-renewal and pluripotency, stem cells possess untold potential for revolutionizing the field of regenerative medicine through the development of novel therapeutic strategies for treating cancer, diabetes, cardiovascular and neurodegenerative diseases. Central to developing these strategies is improving our understanding of biological mechanisms responsible for governing stem cell fate and self-renewal. Increasing attention is being given to the significance of metabolism, through the production of energy and generation of small molecules, as a critical regulator of stem cell functioning...
April 2015: Frontiers in Biology
https://www.readbyqxmd.com/read/25821458/transcriptional-regulation-of-secretory-capacity-by-bzip-transcription-factors
#18
Rebecca M Fox, Deborah J Andrew
Cells of specialized secretory organs expand their secretory pathways to accommodate the increased protein load necessary for their function. The endoplasmic reticulum (ER), the Golgi apparatus and the secretory vesicles, expand not only the membrane components but also the protein machinery required for increased protein production and transport. Increased protein load causes an ER stress response akin to the Unfolded Protein Response (UPR). Recent work has implicated several bZip transcription factors in the regulation of protein components of the early secretory pathway necessary to alleviate this stress...
February 1, 2015: Frontiers in Biology
https://www.readbyqxmd.com/read/25774193/nucleotide-sequence-conservation-of-novel-and-established-cis-regulatory-sites-within-the-tyrosine-hydroxylase-gene-promoter
#19
Meng Wang, Kasturi Banerjee, Harriet Baker, John W Cave
Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis and its gene proximal promoter ( < 1 kb upstream from the transcription start site) is essential for regulating transcription in both the developing and adult nervous systems. Several putative regulatory elements within the TH proximal promoter have been reported, but evolutionary conservation of these elements has not been thoroughly investigated. Since many vertebrate species are used to model development, function and disorders of human catecholaminergic neurons, identifying evolutionarily conserved transcription regulatory mechanisms is a high priority...
February 1, 2015: Frontiers in Biology
https://www.readbyqxmd.com/read/25691893/neural-regulation-of-cns-angiogenesis-during-development
#20
Shang Ma, Zhen Huang
Vertebrates have evolved a powerful vascular system that involves close interactions between blood vessels and target tissues. Vascular biology had been mostly focused on the study of blood vessels for decades, which has generated large bodies of knowledge on vascular cell development, function and pathology. We argue that the prime time has arrived for vascular research on vessel-tissue interactions, especially target tissue regulation of vessel development. The central nervous system (CNS) requires a highly efficient vascular system for oxygen and nutrient transport as well as waste disposal...
February 2015: Frontiers in Biology
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