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https://www.readbyqxmd.com/read/28978834/molecular-biology-and-treatment-of-cml
#1
Shinya Kimura
Since the development of imatinib mesylate, an ABL tyrosine kinase inhibitor (TKI), the treatment of chronic myeloid leukemia (CML) has made remarkable progress. Second and third generation TKIs have also become available for clinical use. Considering the improved treatment outcomes, chronic phase CML has become manageable, with a low mortality rate. Furthermore, clinical trials such as STIM and DADI have shown that TKI can be discontinued safely in certain CML patients. However, some CML patients, especially those in accelerated phase (AP) or blast phase (BP), require more aggressive forms of treatment such as allogenic hematopoietic stem cell transplantation...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28974198/integrated-pipeline-for-inferring-the-evolutionary-history-of-a-gene-family-embedded-in-the-species-tree-a-case-study-on-the-stimate-gene-family
#2
Jia Song, Sisi Zheng, Nhung Nguyen, Youjun Wang, Yubin Zhou, Kui Lin
BACKGROUND: Because phylogenetic inference is an important basis for answering many evolutionary problems, a large number of algorithms have been developed. Some of these algorithms have been improved by integrating gene evolution models with the expectation of accommodating the hierarchy of evolutionary processes. To the best of our knowledge, however, there still is no single unifying model or algorithm that can take all evolutionary processes into account through a stepwise or simultaneous method...
October 3, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28965919/pulsed-electromagnetic-fields-inhibit-human-osteoclast-formation-and-gene-expression-via-osteoblasts
#3
Zhiming He, Nagarajan Selvamurugan, Johanna Warshaw, Nicola C Partridge
Pulsed electromagnetic fields (PEMFs) can be effective in promoting the healing of delayed union or nonunion fractures. We previously reported that PEMF (Spinal-Stim® by Orthofix, Inc., Lewisville, TX) stimulated proliferation, differentiation and mineralization of rat calvarial osteoblastic cells in culture. In the present work we investigated the effects of PEMF (Physio-Stim® by Orthofix, Inc., Lewisville, TX) on human bone marrow macrophages (hBMMs) differentiated to osteoclasts. PEMF had striking inhibitory effects on formation of osteoclasts from hBMMs from both younger and older women...
September 28, 2017: Bone
https://www.readbyqxmd.com/read/28951797/earlier-intervention-with-deep-brain-stimulation-for-parkinson-s-disease
#4
REVIEW
Gerson Suarez-Cedeno, Jessika Suescun, Mya C Schiess
Neuromodulation of subcortical areas of the brain as therapy to reduce Parkinsonian motor symptoms was developed in the mid-twentieth century and went through many technical and scientific advances that established specific targets and stimulation parameters. Deep Brain Stimulation (DBS) was approved by the FDA in 2002 as neuromodulation therapy for advanced Parkinson's disease, prompting several randomized controlled trials that confirmed its safety and effectiveness. The implantation of tens of thousands of patients in North America and Europe ignited research into its potential role in early disease stages and the therapeutic benefit of DBS compared to best medical therapy...
2017: Parkinson's Disease
https://www.readbyqxmd.com/read/28930597/the-store-operated-calcium-channels-in-cancer-metastasis-from-cell-migration-invasion-to-metastatic-colonization
#5
Pingli Mo, Shengyu Yang
Store-operated calcium entry (SOCE) is the predominant calcium entry mechanism in most cancer cells. SOCE is mediated by the endoplasmic reticulum calcium sensor STIMs (STIM1 and 2) and plasma membrane channel forming unit Orais (Orai 1-3). In recent years there is increasing evidence indicating that SOCE in cancer cells is dysregulated to promote cancer cell migration, invasion and metastasis. The overexpression of STIM and Orai proteins has been reported to correlate with the metastatic progression of various cancers...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28919499/ultrasound-guidance-for-phenol-neurolysis-to-the-musculocutaneous-nerve
#6
Mary E Matsumoto, Jessica Berry, Herbie Yung, Martha Matsumoto, Michael C Munin
OBJECTIVE: This study compared electrical stimulation only (e-stim) to ultrasound with e-stim (US) guidance in phenol neurolysis of the musculocutaneous nerve (MCN) for elbow flexor spasticity. We also evaluated the US appearance of MCN in this population. DESIGN: Retrospective review SETTING: University hospital outpatient clinic PARTICIPANTS: Adult patients (N=167) receiving phenol neurolysis of the MCN for treatment of elbow flexor spasticity between 1997 to 2014 and adult control subjects...
September 14, 2017: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/28912430/stim1-dependent-ca-2-signaling-regulates-podosome-formation-to-facilitate-cancer-cell-invasion
#7
Yun-Wen Chen, Yih-Fung Chen, Wen-Tai Chiu, Hong-Chen Chen, Meng-Ru Shen
The clinical significance of STIM proteins and Orai Ca(2+) channels in tumor progression has been demonstrated in different types of cancers. Podosomes are dynamic actin-rich cellular protrusions that facilitate cancer cell invasiveness by degrading extracellular matrix. Whether STIM1-dependent Ca(2+) signaling facilitates cancer cell invasion through affecting podosome formation remains unclear. Here we show that the invasive fronts of cancer tissues overexpress STIM1, accompanied by active store-operated Ca(2+) entry (SOCE)...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900932/neurological-and-motor-disorders-neuronal-store-operated-ca-2-signaling-an-overview-and-its-function
#8
Sunitha Bollimuntha, Biswaranjan Pani, Brij B Singh
Calcium (Ca(2+)) is a ubiquitous second messenger that performs significant physiological task such as neurosecretion, exocytosis, neuronal growth/differentiation, and the development and/or maintenance of neural circuits. An important regulatory aspect of neuronal Ca(2+) homeostasis is store-operated Ca(2+) entry (SOCE) which, in recent years, has gained much attention for influencing a variety of nerve cell responses. Essentially, activation of SOCE ensues following the activation of the plasma membrane (PM) store-operated Ca(2+) channels (SOCC) triggered by the depletion of endoplasmic reticulum (ER) Ca(2+) stores...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900927/cardiovascular-and-hemostatic-disorders-role-of-stim-and-orai-proteins-in-vascular-disorders
#9
Jyoti Tanwar, Mohamed Trebak, Rajender K Motiani
Store-operated Ca(2+) entry (SOCE) mediated by STIM and Orai proteins is a highly regulated and ubiquitous signaling pathway that plays an important role in various cellular and physiological functions. Endoplasmic reticulum (ER) serves as the major site for intracellular Ca(2+) storage. Stromal Interaction Molecule 1/2 (STIM1/2) sense decrease in ER Ca(2+) levels and transmits the message to plasma membrane Ca(2+) channels constituted by Orai family members (Orai1/2/3) resulting in Ca(2+) influx into the cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900924/tissue-specificity-store-operated-ca-2-entry-in-cardiac-myocytes
#10
Martin D Bootman, Katja Rietdorf
Calcium (Ca(2+)) is a key regulator of cardiomyocyte contraction. The Ca(2+) channels, pumps, and exchangers responsible for the cyclical cytosolic Ca(2+) signals that underlie contraction are well known. In addition to those Ca(2+) signaling components responsible for contraction, it has been proposed that cardiomyocytes express channels that promote the influx of Ca(2+) from the extracellular milieu to the cytosol in response to depletion of intracellular Ca(2+) stores. With non-excitable cells, this store-operated Ca(2+) entry (SOCE) is usually easily demonstrated and is essential for prolonging cellular Ca(2+) signaling and for refilling depleted Ca(2+) stores...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900921/the-role-of-mitochondria-in-the-activation-maintenance-of-soce-the-contribution-of-mitochondrial-ca-2-uptake-mitochondrial-motility-and-location-to-store-operated-ca-2-entry
#11
Roland Malli, Wolfgang F Graier
In most cell types, the depletion of internal Ca(2+) stores triggers the activation of Ca(2+) entry. This crucial phenomenon is known since the 1980s and referred to as store-operated Ca(2+) entry (SOCE). With the discoveries of the stromal-interacting molecules (STIMs) and the Ca(2+)-permeable Orai channels as the long-awaited molecular constituents of SOCE, the role of mitochondria in controlling the activity of this particular Ca(2+) entry pathway is kind of buried in oblivion. However, the capability of mitochondria to locally sequester Ca(2+) at sites of Ca(2+) release and entry was initially supposed to rule SOCE by facilitating the Ca(2+) depletion of the endoplasmic reticulum and removing entering Ca(2+) from the Ca(2+)-inhibitable channels, respectively...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900920/the-role-of-mitochondria-in-the-activation-maintenance-of-soce-membrane-contact-sites-as-signaling-hubs-sustaining-store-operated-ca-2-entry
#12
Nicolas Demaurex, Daniele Guido
Store-operated Ca(2+) entry (SOCE) is a cell signaling pathway essential for immune and muscle function controlled by dynamic interactions between Ca(2+)-sensing STIM proteins on the endoplasmic reticulum (ER) and Ca(2+)-permeable ORAI channels on the plasma membrane (PM). STIM-ORAI interactions occur at membrane contact sites (MCS), evolutionarily conserved cellular structures characterized by the close apposition (10-20 nm) between the ER and target membranes that facilitate the exchange of lipids by non-vesicular transport mechanisms...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900918/new-aspects-of-the-contribution-of-er-to-soce-regulation-trpc-proteins-as-a-link-between-plasma-membrane-ion-transport-and-intracellular-ca-2-stores
#13
Alexis Bavencoffe, Michael Xi Zhu, Jin-Bin Tian
Transient receptor potential canonical (TRPC) proteins were identified as molecular candidates of receptor- and/or store-operated channels because of their close homology to the Drosophila TRP and TRPL. Functional studies have revealed that TRPC channels play an integrated part of phospholipase C-transduced cell signaling, mediating the influx of both Ca(2+) and Na(+) into cells. As a consequence, the TRPC channels have diverse functional roles in different cell types, including metabotropic receptor-evoked membrane depolarization and intracellular Ca(2+) concentration elevation...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900915/stim-trp-pathways-and-microdomain-organization-auxiliary-proteins-of-the-stim-orai-complex
#14
Jonathan Pacheco, Luis Vaca
The basic paradigm of a mechanism for calcium influx triggered after a reduction on calcium store content implies a sensor of calcium concentration on the endoplasmic reticulum (the stores) and a calcium channel immersed on the plasma membrane. These two basic components are STIM and Orai, the most fundamental and minimal molecular constituents of the store-operated calcium entry mechanism. However, even when minimal components can be reduced to these two proteins, the intricate process involved in approximating two cellular membranes (endoplasmic reticulum, ER and plasma membrane, PM) require the participation of several other components, many of which remain unidentified to this date...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900914/stim-trp-pathways-and-microdomain-organization-contribution-of-trpc1-in-store-operated-ca-2-entry-impact-on-ca-2-signaling-and-cell-function
#15
Hwei Ling Ong, Indu S Ambudkar
Store-operated calcium entry (SOCE) is a ubiquitous Ca(2+) entry pathway that is activated in response to depletion of ER-Ca(2+) stores and critically controls the regulation of physiological functions in a wide variety of cell types. The transient receptor potential canonical (TRPC) channels (TRPCs 1-7), which are activated by stimuli leading to PIP2 hydrolysis, were first identified as molecular components of SOCE channels. While TRPC1 was associated with SOCE and regulation of function in several cell types, none of the TRPC members displayed I CRAC, the store-operated current identified in lymphocytes and mast cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900913/stim-trp-pathways-and-microdomain-organization-ca-2-influx-channels-the-orai-stim1-trpc-complexes
#16
Dora Bodnar, Woo Young Chung, Dongki Yang, Jeong Hee Hong, Archana Jha, Shmuel Muallem
Ca(2+) influx by plasma membrane Ca(2+) channels is the crucial component of the receptor-evoked Ca(2+) signal. The two main Ca(2+) influx channels of non-excitable cells are the Orai and TRPC families of Ca(2+) channels. These channels are activated in response to cell stimulation and Ca(2+) release from the endoplasmic reticulum (ER). The protein that conveys the Ca(2+) content of the ER to the plasma membrane is the ER Ca(2+) sensor STIM1. STIM1 activates the Orai channels and is obligatory for channel opening...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900912/the-stim-orai-pathway-light-operated-ca-2-entry-through-engineered-crac-channels
#17
Guolin Ma, Shufan Wen, Yun Huang, Yubin Zhou
Ca(2+) signals regulate a plethora of cellular functions that include muscle contraction, heart beating, hormone secretion, lymphocyte activation, gene expression, and metabolism. To study the impact of Ca(2+) signals on biological processes, pharmacological tools and caged compounds have been commonly applied to induce fluctuations of intracellular Ca(2+) concentrations. These conventional approaches, nonetheless, lack rapid reversibility and high spatiotemporal resolution. To overcome these disadvantages, we and others have devised a series of photoactivatable genetically encoded Ca(2+) actuators (GECAs) by installing light sensitivities into a bona fide highly selective Ca(2+) channel, the Ca(2+) release-activated Ca(2+) (CRAC) channel...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900911/the-stim-orai-pathway-regulation-of-stim-and-orai-by-thiol-modifications
#18
Barbara A Niemeyer
Cysteines are among the least abundant amino acids found in proteins. Due to their unique nucleophilic thiol group, they are able to undergo a broad range of chemical modifications besides their known role in disulfide formation, such as S-sulfenylation (-SOH), S-sulfinylation (-SO(2)H), S-sufonylation (-SO(3)H), S-glutathionylation (-SSG), and S-sulfhydration (-SSH), among others. These posttranslational modifications can be irreversible and act as transitional modifiers or as reversible on-off switches for the function of proteins...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900910/the-stim-orai-pathway-conformational-coupling-between-stim-and-orai-in-the-activation-of-store-operated-ca-2-entry
#19
Robert M Nwokonko, Xiangyu Cai, Natalia A Loktionova, Youjun Wang, Yandong Zhou, Donald L Gill
Store-operated Ca(2+) entry fulfills a crucial role in controlling Ca(2+) signals in almost all cells. The Ca(2+)-sensing stromal interaction molecule (STIM) proteins in the endoplasmic reticulum (ER) undergo complex conformational changes in response to depleted ER luminal Ca(2+), allowing them to unfold and become trapped in ER-plasma membrane (PM) junctions. Dimers of STIM proteins trap and gate the plasma membrane Orai Ca(2+) channels within these junctions to generate discrete zones of high Ca(2+) and regulate sensitive Ca(2+)-dependent intracellular signaling pathways...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900909/the-stim-orai-pathway-the-interactions-between-stim-and-orai
#20
Marc Fahrner, Rainer Schindl, Martin Muik, Isabella Derler, Christoph Romanin
A primary Ca(2+) entry pathway in non-excitable cells is established by the Ca(2+) release-activated Ca(2+) channels. Their two limiting molecular components include the Ca(2+)-sensor protein STIM1 located in the endoplasmic reticulum and the Orai channel in the plasma membrane. STIM1 senses the luminal Ca(2+) content, and store depletion induces its oligomerization into puncta-like structures, thereby triggering coupling to as well as activation of Orai channels. A C-terminal STIM1 domain is assumed to couple to both C- and N-terminal, cytosolic strands of Orai, accomplishing gating of the channel...
2017: Advances in Experimental Medicine and Biology
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