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https://www.readbyqxmd.com/read/28749478/molecular-autopsy-in-maternal-fetal-medicine
#1
Hanan E Shamseldin, Wesam Kurdi, Fatima Almusafri, Maha Alnemer, Alya Alkaff, Zeneb Babay, Amal Alhashem, Maha Tulbah, Nada Alsahan, Rubina Khan, Bahauddin Sallout, Elham Al Mardawi, Mohamed Zain Seidahmed, Niema Meriki, Yasser Alsaber, Alya Qari, Ola Khalifa, Wafaa Eyaid, Zuhair Rahbeeni, Ahmed Kurdi, Mais Hashem, Tarfa Alshidi, Eman Al-Obeid, Firdous Abdulwahab, Niema Ibrahim, Nour Ewida, Karen El-Akouri, Mariam Al Mulla, Tawfeg Ben-Omran, Matthias Pergande, Sebahattin Cirak, Saeed Al Tala, Ranad Shaheen, Eissa Faqeih, Fowzan S Alkuraya
PurposeThe application of genomic sequencing to investigate unexplained death during early human development, a form of lethality likely enriched for severe Mendelian disorders, has been limited.MethodsIn this study, we employed exome sequencing as a molecular autopsy tool in a cohort of 44 families with at least one death or lethal fetal malformation at any stage of in utero development. Where no DNA was available from the fetus, we performed molecular autopsy by proxy, i.e., through parental testing.ResultsPathogenic or likely pathogenic variants were identified in 22 families (50%), and variants of unknown significance were identified in further 15 families (34%)...
July 27, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28731145/piezo1-protein-induces-the-apoptosis-of-human-osteoarthritis-derived-chondrocytes-by-activating-caspase-12-the-signaling-marker-of-er-stress
#2
Xiao-Fei Li, Zhao Zhang, Zhu-Ke Chen, Zhao-Wei Cui, Hai-Ning Zhang
The present study was carried out to determine whether the mechanically activated cation channel Piezo1 protein plays a role as a signaling pathway which causes the apoptosis of human chondrocytes. The chondrocytes were isolated, cultured, and then subjected to mechanical stretch force for 0, 2, 12, 24 and 48 h, respectively. The expression levels of Piezo1 and the apoptosis-related protein caspase-12 were assessed by reverse transcription-quantitative polymerase chain reaction, as well as the apoptosis-related genes, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-associated X protein (Bax) and Bcl-2-associated death promoter (BAD)...
September 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28728825/genetic-diseases-of-piezo1-and-piezo2-dysfunction
#3
S L Alper
Mutations in the genes encoding the mechanosensitive cation channels PIEZO1 and PIEZO2 are responsible for multiple hereditary human diseases. Loss-of-function mutations in the human PIEZO1 gene cause autosomal recessive congenital lymphatic dysplasia. Gain-of-function mutations in the human PIEZO1 gene cause the autosomal dominant hemolytic anemia, hereditary xerocytosis (also known as dehydrated stomatocytosis). Loss-of-function mutations in the human PIEZO2 gene cause an autosomal recessive syndrome of muscular atrophy with perinatal respiratory distress, arthrogryposis, and scoliosis...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28728823/piezo1-channels-in-vascular-development-and-the-sensing-of-shear-stress
#4
A J Hyman, S Tumova, D J Beech
A critical point in mammalian development occurs before mid-embryogenesis when the heart starts to beat, pushing blood into the nascent endothelial lattice. This pushing force is a signal, detected by endothelial cells as a frictional force (shear stress) to trigger cellular changes that underlie the essential processes of vascular remodeling and expansion required for embryonic growth. The processes are complex and multifactorial and Piezo1 became a recognized player only 2years ago, 4years after Piezo1's initial discovery as a functional membrane protein...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28728822/a-microfluidic-approach-for-studying-piezo-channels
#5
M M Maneshi, P A Gottlieb, S Z Hua
Microfluidics is an interdisciplinary field intersecting many areas in engineering. Utilizing a combination of physics, chemistry, biology, and biotechnology, along with practical applications for designing devices that use low volumes of fluids to achieve high-throughput screening, is a major goal in microfluidics. Microfluidic approaches allow the study of cells growth and differentiation using a variety of conditions including control of fluid flow that generates shear stress. Recently, Piezo1 channels were shown to respond to fluid shear stress and are crucial for vascular development...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28728821/the-kinetics-and-the-permeation-properties-of-piezo-channels
#6
R Gnanasambandam, P A Gottlieb, F Sachs
Piezo channels are eukaryotic, cation-selective mechanosensitive channels (MSCs), which show rapid activation and voltage-dependent inactivation. The kinetics of these channels are largely consistent across multiple cell types and different stimulation paradigms with some minor variability. No accessory subunits that associate with Piezo channels have been reported. They are homotrimers and each ∼300kD monomer has an N-terminal propeller blade-like mechanosensing module, which can confer mechanosensing capabilities on ASIC-1 (the trimeric non-MSC, acid-sensing ion channel-1) and a C-terminal pore module, which influences conductance, selectivity, and channel inactivation...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28728820/role-of-piezo-channels-in-joint-health-and-injury
#7
W Lee, F Guilak, W Liedtke
Cartilage is an intrinsically mechanically sensitive tissue composed of chondrocytes as the only cell type. Chondrocyte mechanotransduction is not well understood, but recently we identified critical components of the mechanotransduction machinery demonstrating how mechanical stimulation of these cells can be converted into cellular calcium signals. Physiologic mechanical cues induce anabolic responses of (post-mitotic) chondrocytes via transient receptor potential vanilloid 4 ion channels, whereas injurious mechanical stress is transduced by Piezo1 jointly with Piezo2 ion channels...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28728819/regulation-of-piezo-channels-by-cellular-signaling-pathways
#8
I Borbiro, T Rohacs
The recently identified mechanically activated Piezo1 and Piezo2 channels play major roles in various aspects of mechanosensation in mammals, and their mutations are associated with human diseases. Recent reports show that activation of cell surface receptors coupled to heterotrimeric Gq proteins increase the sensitivity of Piezo2 channels to mechanical stimuli. Activation of the cyclic adenosine monophosphate pathway was also shown to potentiate Piezo2 channel activity. This phenomenon may play a role in mechanical allodynia or hyperalgesia during inflammation...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28728818/mechanosensitive-piezo-channels-in-the-gastrointestinal-tract
#9
C Alcaino, G Farrugia, A Beyder
Sensation of mechanical forces is critical for normal function of the gastrointestinal (GI) tract and abnormalities in mechanosensation are linked to GI pathologies. In the GI tract there are several mechanosensitive cell types-epithelial enterochromaffin cells, intrinsic and extrinsic enteric neurons, smooth muscle cells and interstitial cells of Cajal. These cells use mechanosensitive ion channels that respond to mechanical forces by altering transmembrane ionic currents in a process called mechanoelectrical coupling...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28728817/piezo2-in-cutaneous-and-proprioceptive-mechanotransduction-in-vertebrates
#10
E O Anderson, E R Schneider, S N Bagriantsev
Mechanosensitivity is a fundamental physiological capacity, which pertains to all life forms. Progress has been made with regard to understanding mechanosensitivity in bacteria, flies, and worms. In vertebrates, however, the molecular identity of mechanotransducers in somatic and neuronal cells has only started to appear. The Piezo family of mechanogated ion channels marks a pivotal milestone in understanding mechanosensitivity. Piezo1 and Piezo2 have now been shown to participate in a number of processes, ranging from arterial modeling to sensing muscle stretch...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28728816/in-touch-with-the-mechanosensitive-piezo-channels-structure-ion-permeation-and-mechanotransduction
#11
J Geng, Q Zhao, T Zhang, B Xiao
Mechanotransduction, the conversion of mechanical forces into biological signals, plays critical roles in various physiological and pathophysiological processes in mammals, such as conscious sensing of touch, pain, and sound, as well as unconscious sensing of blood flow-associated shear stress, urine flow, and bladder distention. Among the various molecules involved in mechanotransduction, mechanosensitive (MS) cation channels have long been postulated to represent one critical class of mechanotransducers that directly and rapidly converts mechanical force into electrochemical signals...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28728815/the-structural-basis-for-sensing-by%C3%A2-the-piezo1-protein
#12
W Li, N Gao, M Yang
Mechanotransduction is one of the processes by which cells sense and convert mechanical stimuli into biological signals. Experimental data from various species have revealed crucial roles for mechanotransduction in organ development and a plethora of physiological activities. Piezo proteins have recently been identified as the long-sought-after mechanically activated cation channels in eukaryotes. The architecture of mouse Piezo1 (mPiezo1) channel determined by cryoelectron microscopic single-particle analysis at medium resolution yielded important insights into the mechanical force sensing mechanism...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28728814/a-tour-de-force-the-discovery-properties-and-function-of-piezo-channels
#13
P A Gottlieb
Mechanical transducers appear throughout cell biology and are used to convert mechanical stress into chemical or electrical signals that allow the cell to respond to environmental changes. In the past six years, a eukaryotic mechanical channel family with two members, Piezo1 and Piezo2, has been identified. Piezo1 was shown to be a cation-selective channel that does not require ancillary proteins for activity. Mouse Piezo1 is large, with over 2500 amino acids, and is not homologous to other ion channels. Both piezo channels have rapid voltage-dependent inactivation with a reversal potential near 0mV...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28716860/novel-mechanisms-of-piezo1-dysfunction-in-hereditary-xerocytosis
#14
Edyta Glogowska, Eve R Schneider, Yelena Maksimova, Vincent P Schulz, Kimberly Lezon-Geyda, John Wu, Kottayam Radhakrishnan, Siobán B Keel, Donald Mahoney, Alison M Freidmann, Rachel A Altura, Elena O Gracheva, Sviatoslav N Bagriantsev, Theodosia A Kalfa, Patrick G Gallagher
Mutations in PIEZO1 are the primary cause of hereditary xerocytosis, a clinically heterogeneous, dominantly inherited disorder of erythrocyte dehydration. We utilized next generation sequencing-based techniques to identify PIEZO1 mutations in individuals from 9 kindreds referred with suspected HX and/or undiagnosed congenital hemolytic anemia. Mutations were primarily found in the highly conserved, COOH-terminal pore region domain. Several mutations were novel and demonstrated ethnic specificity. We characterized these mutations using genomic, bioinformatic, cell biology, and physiology-based functional assays...
July 17, 2017: Blood
https://www.readbyqxmd.com/read/28705727/the-piezo1-protein-ion-channel-functions-in-human-nucleus-pulposus-cell-apoptosis-by-regulating-mitochondrial-dysfunction-and-the-endoplasmic-reticulum-stress-signal-pathway
#15
Xiao-Fei Li, Ping Leng, Zhao Zhang, Hai-Ning Zhang
The Piezo1 protein ion channel is a novel mechanical stretch-activated ion channel (SAC) closely related to mechanical signals. Mechanotransduction plays a crucial role in organ development and homeostasis. Previous studies identified Piezo1 and demonstrated that it is distinct from other ion channels with well-established roles in lower organisms. Mechanical stretch-activated ion channels from other organisms are not conserved in mammals or do not act as mechanically activated channels in mammals. In the current study, we explored the role of the Piezo1 ion channel in human nucleus pulposus cell (NP cell) apoptosis through mechanical force-induced mitochondrial dysfunction and endoplasmic reticulum stress...
July 10, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28698554/chondroprotection-by-urocortin-involves-blockade-of-the-mechanosensitive-ion-channel-piezo1
#16
K M Lawrence, R C Jones, T R Jackson, R L Baylie, B Abbott, B Bruhn-Olszewska, T N Board, I C Locke, S M Richardson, P A Townsend
Osteoarthritis (OA) is characterised by progressive destruction of articular cartilage and chondrocyte cell death. Here, we show the expression of the endogenous peptide urocortin1 (Ucn1) and two receptor subtypes, CRF-R1 and CRF-R2, in primary human articular chondrocytes (AC) and demonstrate its role as an autocrine/paracrine pro-survival factor. This effect could only be removed using the CRF-R1 selective antagonist CP-154526, suggesting Ucn1 acts through CRF-R1 when promoting chondrocyte survival. This cell death was characterised by an increase in p53 expression, and cleavage of caspase 9 and 3...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28676421/how-cells-channel-their-stress-interplay-between-piezo1-and-the-cytoskeleton
#17
REVIEW
Jamison L Nourse, Medha M Pathak
Cells constantly encounter mechanical stimuli in their environment, such as dynamic forces and mechanical features of the extracellular matrix. These mechanical cues are transduced into biochemical signals, and integrated with genetic and chemical signals to modulate diverse physiological processes. Cells also actively generate forces to internally transport cargo, such as vesicles and organelles, to explore the physical properties of their environment and to spatially position themselves and other cells during development...
July 1, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28670382/stretch-activated-channel-piezo1-is-up-regulated-in-failure-heart-and-cardiomyocyte-stimulated-by-angii
#18
Jianlin Liang, Boshui Huang, Guiyi Yuan, Ying Chen, Fasheng Liang, Huayuan Zeng, Shaoxin Zheng, Liang Cao, Dengfeng Geng, Shuxian Zhou
Mechanotransduction is the conversion of extracellular mechanical stimuli into intracellular biochemical signals, and plays an important role in heart responses to its own mechanical environment. Piezo1 as a distinct stretch-activated channel (SAC) in mammal involves in not only vascular remodeling during embryonic development but also arterial remodeling upon to hypertension at adult stage. In the present study, the expression of Piezo1 was up-regulated in failure heart induced by myocardial infarction (MI) by real-time PCR, Western blot and immunohistochemistry analysis...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28647645/adding-dimension-to-cellular-mechanotransduction-advances-in-biomedical-engineering-of-multiaxial-cell-stretch-systems-and-their-application-to-cardiovascular-biomechanics-and-mechano-signaling
#19
REVIEW
O Friedrich, D Schneidereit, Y A Nikolaev, V Nikolova-Krstevski, S Schürmann, A Wirth-Hücking, A L Merten, D Fatkin, B Martinac
Hollow organs (e.g. heart) experience pressure-induced mechanical wall stress sensed by molecular mechano-biosensors, including mechanosensitive ion channels, to translate into intracellular signaling. For direct mechanistic studies, stretch devices to apply defined extensions to cells adhered to elastomeric membranes have stimulated mechanotransduction research. However, most engineered systems only exploit unilateral cellular stretch. In addition, it is often taken for granted that stretch applied by hardware translates 1:1 to the cell membrane...
June 21, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28636944/transduction-of-repetitive-mechanical-stimuli-by-piezo1-and-piezo2-ion-channels
#20
Amanda H Lewis, Alisa F Cui, Malcolm F McDonald, Jörg Grandl
Several cell types experience repetitive mechanical stimuli, including vein endothelial cells during pulsating blood flow, inner ear hair cells upon sound exposure, and skin cells and their innervating dorsal root ganglion (DRG) neurons when sweeping across a textured surface or touching a vibrating object. While mechanosensitive Piezo ion channels have been clearly implicated in sensing static touch, their roles in transducing repetitive stimulations are less clear. Here, we perform electrophysiological recordings of heterologously expressed mouse Piezo1 and Piezo2 responding to repetitive mechanical stimulations...
June 20, 2017: Cell Reports
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