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https://www.readbyqxmd.com/read/29323106/sequential-forward-and-reverse-transport-of-the-na-ca2-exchanger-generates-ca2-oscillations-within-mitochondria
#1
Krishna Samanta, Gary R Mirams, Anant B Parekh
Mitochondrial Ca2+ homoeostasis regulates aerobic metabolism and cell survival. Ca2+ flux into mitochondria is mediated by the mitochondrial calcium uniporter (MCU) channel whereas Ca2+ export is often through an electrogenic Na+-Ca2+ exchanger. Here, we report remarkable functional versatility in mitochondrial Na+-Ca2+ exchange under conditions where mitochondria are depolarised. Following physiological stimulation of cell-surface receptors, mitochondrial Na+-Ca2+ exchange initially operates in reverse mode, transporting cytosolic Ca2+ into the matrix...
January 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/29316654/exercise-and-mitochondrial-dynamics-keeping-in-shape-with-ros-and-ampk
#2
REVIEW
Adam J Trewin, Brandon J Berry, Andrew P Wojtovich
Exercise is a robust stimulus for mitochondrial adaptations in skeletal muscle which consequently plays a central role in enhancing metabolic health. Despite this, the precise molecular events that underpin these beneficial effects remain elusive. In this review, we discuss molecular signals generated during exercise leading to altered mitochondrial morphology and dynamics. In particular, we focus on the interdependence between reactive oxygen species (ROS) and redox homeostasis, the sensing of cellular bioenergetic status via 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK), and the regulation of mitochondrial fission and fusion...
January 6, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29312603/intratumoral-heterogeneity-and-tert-promoter-mutations-in-progressive-higher-grade-meningiomas
#3
Tareq A Juratli, Christian Thiede, Mara V A Koerner, Shilpa S Tummala, Dirk Daubner, Ganesh M Shankar, Erik A Williams, Maria Martinez-Lage, Silke Soucek, Katja Robel, Tristan Penson, Mechthild Krause, Steffen Appold, Matthias Meinhardt, Thomas Pinzer, Julie J Miller, Dietmar Krex, Heather A Ely, Ian M Silverman, Jason Christiansen, Gabriele Schackert, Hiroaki Wakimoto, Matthias Kirsch, Priscilla K Brastianos, Daniel P Cahill
Background: Recent studies have reported mutations in the telomerase reverse transcriptase promoter (TERTp) in meningiomas. We sought to determine the frequency, clonality and clinical significance of telomere gene alterations in a cohort of patients with progressive/higher-grade meningiomas. Methods: We characterized 64 temporally- and regionally-distinct specimens from 26 WHO grade III meningioma patients. On initial diagnoses, the meningiomas spanned all WHO grades (3 grade I, 13 grade II and 10 grade III)...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29301345/eicosanoid-diversity-of-stony-corals
#4
Helike Lõhelaid, Nigulas Samel
Oxylipins are well-established lipid mediators in plants and animals. In mammals, arachidonic acid (AA)-derived eicosanoids control inflammation, fever, blood coagulation, pain perception and labor, and, accordingly, are used as drugs, while lipoxygenases (LOX), as well as cyclooxygenases (COX) serve as therapeutic targets for drug development. In soft corals, eicosanoids are synthesized on demand from AA by LOX, COX, and catalase-related allene oxide synthase-lipoxygenase (cAOS-LOX) and hydroperoxide lyase-lipoxygenase (cHPL-LOX) fusion proteins...
January 3, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29280261/deproteinized-bovine-bone-matrix-induces-osteoblast-differentiation-via-macrophage-polarization
#5
Miusi Shi, Can Wang, Yulan Wang, Cuizhu Tang, Richard J Miron, Yufeng Zhang
Bone grafts are widely used in bone regeneration to increase the speed and quality of new bone formation. While they are routinely characterized based on their biocompatible and bioactive properties, they also exert a profound impact on host immune responses, which in turn can display a significant effect on the healing and repair process. In this study, we investigated the role of macrophage behavior on deproteinized bovine bone matrix (DBBM, BioOss) to investigate their impact on creating either a pro- or anti-inflammatory micro-environment for tissue integration...
December 27, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29277318/t2e-tmprss2-erg-fusion-transcripts-are-associated-with-higher-levels-of-amacr-mrna-and-a-subsequent-prostate-cancer-diagnosis-in-patients-with-atypical-small-acinar-proliferation
#6
Isil Ezgi Eryilmaz, Yakup Kordan, Berna Aytac Vuruskan, Onur Kaygısız, Berrin Tunca, Gulsah Cecener
Genetic rearrangements involving androgen-regulated transmembrane protease serine 2 (TMPRSS2) and genes from the ETS transcription factor family, most commonly ERG and ETV1, result in alteration that responsible for oncogenic activity in prostate cancer (PC). The aims of the present study were to: 1) investigate the frequency of these fusion transcripts in prostate tissue samples obtained from patients diagnosed with atypical small acinar proliferation (ASAP), 2) determine any clinical significance of T2E expression at the RNA level in predicting PC detection in subsequent biopsies, and 3) evaluate expression of the PC marker, alpha-methylacyl-CoA racemase (AMACR), according to T2E status by real-time quantitative reverse transcription PCR (RT-qPCR)...
December 22, 2017: Gene
https://www.readbyqxmd.com/read/29259723/effects-of-ctla4-ig-on-human-monocytes
#7
Toshihiro Tono, Satoko Aihara, Takayuki Hoshiyama, Yoshiyuki Arinuma, Tatsuo Nagai, Shunsei Hirohata
Background: Abatacept, a CTLA4-Ig fusion protein attenuates T cell activation by inhibiting the CD80/86-CD28 costimulatory pathway that is required for the proper T cell activation and thus displays beneficial effects in the treatment of rheumatoid arthritis (RA). Although some studies have disclosed the in vitro effects of this biological agent on the immune-competent cells, the precise mechanisms of action in RA still remain unclear. The current studies were therefore undertaken to explore the effects of abatacept on monocytes in detail...
2017: Inflammation and Regeneration
https://www.readbyqxmd.com/read/29251372/synthesis-and-biological-evaluation-of-a-degradable-trehalose-glycopolymer-prepared-by-raft-polymerization
#8
Uland Y Lau, Emma M Pelegri-O'Day, Heather D Maynard
There is a significant need for new biodegradable protein stabilizing polymers. Herein, the synthesis of a polymer with trehalose side chains and hydrolytically degradable backbone esters and its evaluation for protein stabilization and cytotoxicity are described. Specifically, an alkene-containing parent polymer is synthesized by reversible addition-fragmentation chain transfer polymerization, and thiolated trehalose is installed using a radical-initiated thiol-ene reaction. The stabilizing properties of the polymer are investigated by thermally stressing granulocyte colony-stimulating factor (G-CSF), which is expressed and purified using a custom-designed G-CSF fusion protein with a polyhistidine-tagged maltose binding protein...
December 18, 2017: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/29245254/a-primary-gastric-synovial-sarcoma-a-case-report-and-literature-review
#9
REVIEW
In Tae So, Kwang Bum Cho, Ju Yup Lee, Sang Jin Kim, Hye In Jung, Jong Hwan Choi, Yoo Jin Lee, Hyun Jik Lee, Kyung Sik Park, Seung Wan Ryu, Yu Na Kang
RATIONALE: When a gastric spindle cell tumor is observed, the possibility of synovial carcinoma, besides common mesenchymal tumor, should also be considered. PRESENTING CONCERNS OF THE PATIENT: The patient is a 51-year-old American woman who underwent medical check-up at a general hospital. Upper endoscopy showed a 2-cm sized mass covered with intact mucosa, and a central depression located on the posterior wall of the mid body. Biopsy of the mass showed focal atypical cells proliferation in mucosa on hematoxylin & eosin (H&E) staining...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29244700/conversion-of-glenohumeral-fusion-to-reverse-total-shoulder-arthroplasty-a-case-report
#10
C Brian Toney, Matthew J Thompson, Brandon J Barnes, N Douglas Boardman
CASE: A 41-year-old woman presented 5 years after glenohumeral arthrodesis. She experienced symptomatic relief following conversion to reverse total shoulder arthroplasty, regaining nearly full passive range of motion and >50% of normal active forward flexion, abduction, internal rotation, and external rotation. CONCLUSION: Conversion from glenohumeral arthrodesis to reverse total shoulder arthroplasty in a patient with a functioning deltoid and adequate bone stock may provide symptomatic relief and improved function in the setting of symptomatic glenohumeral arthrodesis refractory to conservative measures...
January 2017: JBJS Case Connector
https://www.readbyqxmd.com/read/29237113/the-replication-protein-cdc6-suppresses-centrosome-over-duplication-in-a-manner-independent-of-its-atpase-activity
#11
Gwang Su Kim, Inyoung Lee, Ji Hun Kim, Deog Su Hwang
The Cdc6 protein is essential for the initiation of chromosomal replication and functions as a licensing factor to maintain chromosome integrity. During the S and G2 phases of the cell cycle, Cdc6 has been found to inhibit the recruitment of pericentriolar material (PCM) proteins to the centrosome and to suppress centrosome over-duplication. In this report, we analyzed the correlation between these two functions of Cdc6 at the centrosome. Cdc6 depletion increased the population of cells showing centrosome over-duplication and premature centrosome separation; Cdc6 expression reversed these changes...
December 12, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/29236768/autophagy-induction-by-mycobacterium-indicus-pranii-promotes-mycobacterium-tuberculosis-clearance-from-raw-264-7-macrophages
#12
Bindu Singh, Mohd Saqib, Ananya Gupta, Pawan Kumar, Sangeeta Bhaskar
Mycobacterium indicus pranii (MIP) is a potent vaccine candidate against tuberculosis (TB) as it has demonstrated significant protection in animal models of tuberculosis as well as in clinical trials. Higher protective efficacy of MIP against TB as compared to BCG provoked the efforts to gain insight into the molecular mechanisms underlying MIP mediated protection against Mycobacterium tuberculosis (M.tb). Autophagy, initially described as a cell survival mechanism during starvation, also plays a key role in host resistance to M...
2017: PloS One
https://www.readbyqxmd.com/read/29230030/silica-inhalation-altered-telomere-length-and-gene-expression-of-telomere-regulatory-proteins-in-lung-tissue-of-rats
#13
Mohammad Shoeb, Pius Joseph, Vamsi Kodali, Gul Mustafa, Breanne Y Farris, Christina Umbright, Jenny R Roberts, Aaron Erdely, James M Antonini
Exposure to silica can cause lung fibrosis and cancer. Identification of molecular targets is important for the intervention and/or prevention of silica-induced lung diseases. Telomeres consist of tandem repeats of DNA sequences at the end of chromosomes, preventing chromosomal fusion and degradation. Regulator of telomere length-1 (RTEL1) and telomerase reverse transcriptase (TERT), genes involved in telomere regulation and function, play important roles in maintaining telomere integrity and length. The goal of this study was to assess the effect of silica inhalation on telomere length and the regulation of RTEL1 and TERT...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29224413/low-hox-gene-expression-in-pml-rar%C3%AE-positive-leukemia-results-from-suppressed-histone-demethylation
#14
Kateřina Rejlová, Alena Musilová, Karolina Škvárová Kramarzová, Markéta Žaliová, Karel Fišer, Meritxell Alberich-Jorda, Jan Trka, Júlia Starková
Homeobox (HOX) genes are frequently dysregulated in leukemia. Previous studies have shown that aberrant HOX gene expression accompanies leukemogenesis and affects disease progression and leukemia patient survival. Patients with acute myeloid leukemia (AML) bearing PML-RARα fusion gene has distinct HOX gene signature in comparison to other subtypes of AML patients although the mechanism of transcription regulation is not completely understood. We previously found an association between the mRNA levels of HOX genes and those of the histone demethylases JMJD3 and UTX in PML-RARα- positive leukemia patients...
December 11, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29224278/-clinicopathologic-and-molecular-genetic-characterizations-of-biphenotypic-sinonasal-sarcoma
#15
M Zhao, Q Y LaoI, D H Zhao, J Ma, G Q Ru, X L He, Z Wang, J Wang
Objective: To investigate the clinicopathologic characteristics, immunophenotypes, molecular genetics, and diagnostic and differential diagnostic features of biphenotypic sinonasal sarcoma (BSNS). Methods: Three cases of BSNS were retrieved, the histomorphology, immunophenotype and molecular genetics were analyzed with review of literature. Results: There were 2 male and 1 female patient aged 45, 29 and 40 years, respectively.Computed tomography and magnetic resonance imaging examinations showed a large polypoid mass occupying the sinonasal cavity in all 3 patients...
December 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29220288/contemporary-sarcoma-diagnosis-genetics-and-genomics
#16
Inga-Marie Schaefer, Gregory M Cote, Jason L Hornick
Sarcomas include diverse mesenchymal neoplasms with widely varied prognosis, clinical behavior, and treatment. Owing to their rarity and histologic overlap, accurate diagnosis of sarcomas can be challenging. Our approach has evolved dramatically in the past few decades, where novel insights into the molecular pathogenetic basis for sarcomas has dramatically (re)shaped contemporary diagnosis, building on a largely morphology- and clinical presentation-based strategy. Examples include the introduction of novel immunohistochemical markers that serve as surrogates for molecular genetic alterations and identification of characteristic molecular alterations...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29218031/crispr-cas-systems-in-bacteroides-fragilis-an-important-pathobiont-in-the-human-gut-microbiome
#17
Mehrdad Tajkarimi, Hannah M Wexler
Background: While CRISPR-Cas systems have been identified in bacteria from a wide variety of ecological niches, there are no studies to describe CRISPR-Cas elements in Bacteroides species, the most prevalent anaerobic bacteria in the lower intestinal tract. Microbes of the genus Bacteroides make up ~25% of the total gut microbiome. Bacteroides fragilis comprises only 2% of the total Bacteroides in the gut, yet causes of >70% of Bacteroides infections. The factors causing it to transition from benign resident of the gut microbiome to virulent pathogen are not well understood, but a combination of horizontal gene transfer (HGT) of virulence genes and differential transcription of endogenous genes are clearly involved...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29217280/photosome-membranes-merge-and-organize-tending-towards-rhombohedral-symmetry-when-light-is-emitted
#18
Malika Ouldali, Virginie Maury, Gisèle Nicolas, Jean Lepault
Polynoid worm elytra emit light when mechanically or electrically stimulated. Specialized cells, the photocytes, contain light emitting machineries, the photosomes. Successive stimulations induce light intensity variations and show a coupling within and between photosomes. Here, we describe, using electron tomography of cryo-substituted elytra and freeze-fracturing, the structural transition associated to light emission: undulating tubules come closer, organize and their number forming photosomes increases...
December 4, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/29212658/a-new-mitofusin-topology-places-the-redox-regulated-c-terminus-in-the-mitochondrial-intermembrane-space
#19
Sevan Mattie, Jan Riemer, Jeremy G Wideman, Heidi M McBride
Mitochondrial fusion occurs in many eukaryotes, including animals, plants, and fungi. It is essential for cellular homeostasis, and yet the underlying mechanisms remain elusive. Comparative analyses and phylogenetic reconstructions revealed that fungal Fzo1 and animal Mitofusin proteins are highly diverged from one another and lack strong sequence similarity. Bioinformatic analysis showed that fungal Fzo1 proteins exhibit two predicted transmembrane domains, whereas metazoan Mitofusins contain only a single transmembrane domain...
December 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29212266/ews-fli1-and-rna-helicase-a-interaction-inhibitor-yk-4-279-inhibits-growth-of-neuroblastoma
#20
Wenjing Sun, Yesenia Rojas, Hao Wang, Yang Yu, Yongfeng Wang, Zhenghu Chen, Kimal Rajapakshe, Xin Xu, Wei Huang, Saurabh Agarwal, Roma H Patel, Sarah Woodfield, Yanling Zhao, Jingling Jin, Hong Zhang, Angela Major, M John Hicks, Jason M Shohet, Sanjeev A Vasudevan, Cristian Coarfa, Jianhua Yang, Jed G Nuchtern
Treatment failure in high risk neuroblastoma (NB) is largely due to the development of chemotherapy resistance. We analyzed the gene expression changes associated with exposure to chemotherapy in six high risk NB tumors with the aid of the Connectivity Map bioinformatics platform. Ten therapeutic agents were predicted to have a high probability of reversing the transcriptome changes associated with neoadjuvant chemotherapy treatment. Among these agents, initial screening showed the EWS-FLI1 and RNA helicase A interaction inhibitor YK-4-279, had obvious cytotoxic effects on NB cell lines...
November 7, 2017: Oncotarget
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