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https://www.readbyqxmd.com/read/29352717/should-we-use-cell-of-origin-and-dual-protein-expression-in-treating-dlbcl
#1
REVIEW
Peter A Riedell, Sonali M Smith
Treatment outcomes in diffuse large B-cell lymphoma (DLBCL) following standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy is highly variable and dependent on a number of clinical, biologic, and genetic features. The identification of molecular heterogeneity via gene expression profiling dichotomizes patients based on the cell of origin (COO) model into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subsets, with ABC-DLBCL having a worse outcome...
December 24, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29352609/induction-of-mitophagy-in-the-hei-oc1-auditory-cell-line-and-activation-of-the-atg12-lc3-pathway-in-the-organ-of-corti
#2
Cristian Setz, Anne-Sophie Benischke, Anna Catharina Pinho Ferreira Bento, Yves Brand, Soledad Levano, Franziska Paech, Katharina Leitmeyer, Daniel Bodmer
Autophagy is a highly evolutionary conserved quality control defense mechanism within cells, which has also been implicated in cell death processes. In the mammalian inner ear, autophagy has been shown to play a role during early morphogenesis as well as in adult cochlear hair cells exposed to ototoxic insults. Mitophagy, a selective autophagic cell process targeting mitochondria, hasn't been studied in the inner ear so far. On this work, we searched for molecular indicators of mitophagy within House Ear Institute-Organ of Corti-1 (HEI-OC1) cells as well as in the organ of Corti (OC)...
January 11, 2018: Hearing Research
https://www.readbyqxmd.com/read/29352484/melatonin-ameliorates-a%C3%AE-42-induced-alteration-of-%C3%AE-app-processing-secretases-via-the-melatonin-receptor-through-the-pin1-gsk3%C3%AE-nf-%C3%AE%C2%BAb-pathway-in-sh-sy5y-cells
#3
Vorapin Chinchalongporn, Mayuri Shukla, Piyarat Govitrapong
Melatonin is involved in the physiological regulation of the β- amyloid precursor protein (βAPP) cleaving secretases which are responsible for generation of the neurotoxic amyloid beta (Aβ) peptide, one of the hallmarks of Alzheimer's disease (AD) pathology. In this study, we aimed to determine the underlying mechanisms of this regulation under pathological conditions. We establish that melatonin prevents Aβ42 -induced down-regulation of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) as well as up-regulation of β-site APP-cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) in SH-SY5Y cell cultures...
January 20, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29352300/5-aminosalicylic-acid-improves-lipid-profile-in-mice-fed-a-high-fat-cholesterol-diet-through-its-dual-effects-on-intestinal-ppar%C3%AE-and-ppar%C3%AE
#4
Zheng Wang, Debby Koonen, Marten Hofker, Zhijun Bao
Obesity is associated with a series of metabolic complications, including dyslipidemia and insulin resistance (IR) that lack effective therapies. In recent years, intestinal inflammation has been suggested to contribute to obesity related metabolic syndrome and targeting gut inflammation with 5-ASA improves diet induced IR, however, its role in dyslipidemia is unknown and has never been explored. In the present study, we reported for the first time that administration of 5-ASA for 12 weeks significantly improved lipid profile by repressing plasma triglycerides and free cholesterol levels in mice fed high-fat cholesterol diet (HFC)...
2018: PloS One
https://www.readbyqxmd.com/read/29352225/a-humanized-mouse-model-of-liver-fibrosis-following-expansion-of-transplanted-hepatic-stellate-cells
#5
Daniel Benten, Johannes Kluwe, Jan W Wirth, Nina D Thiele, Antonia Follenzi, Kuldeep K Bhargava, Christopher J Palestro, Michael Koepke, Reni Tjandra, Tassilo Volz, Marc Lutgehetmann, Sanjeev Gupta
Hepatic stellate cells (HSCs) are major contributors to liver fibrosis, as hepatic injuries may cause their transdifferentiation into myofibroblast-like cells capable of producing excessive extracellular matrix proteins. Also, HSCs can modulate engraftment of transplanted hepatocytes and contribute to liver regeneration. Therefore, understanding the biology of human HSCs (hHSCs) is important, but effective methods have not been available to address their fate in vivo. To investigate whether HSCs could engraft and repopulate the liver, we transplanted GFP-transduced immortalized hHSCs into immunodeficient NOD/SCID mice...
January 19, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29351737/identifying-genome-wide-immune-gene-variation-underlying-infectious-disease-in-wildlife-populations-a-next-generation-sequencing-approach-in-the-gopher-tortoise
#6
Jean P Elbers, Mary B Brown, Sabrina S Taylor
BACKGROUND: Infectious disease is the single greatest threat to taxa such as amphibians (chytrid fungus), bats (white nose syndrome), Tasmanian devils (devil facial tumor disease), and black-footed ferrets (canine distemper virus, plague). Although understanding the genetic basis to disease susceptibility is important for the long-term persistence of these groups, most research has been limited to major-histocompatibility and Toll-like receptor genes. To better understand the genetic basis of infectious disease susceptibility in a species of conservation concern, we sequenced all known/predicted immune response genes (i...
January 19, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29351342/a-homozygous-missense-variant-in-vwa2-encoding-an-interactor-of-the-fraser-complex-in-a-patient-with-vesicoureteral-reflux
#7
Amelie T van der Ven, Birgit Kobbe, Stefan Kohl, Shirlee Shril, Hans-Martin Pogoda, Thomas Imhof, Hadas Ityel, Asaf Vivante, Jing Chen, Daw-Yang Hwang, Dervla M Connaughton, Nina Mann, Eugen Widmeier, Mary Taglienti, Johanna Magdalena Schmidt, Makiko Nakayama, Prabha Senguttuvan, Selvin Kumar, Velibor Tasic, Elijah O Kehinde, Shrikant M Mane, Richard P Lifton, Neveen Soliman, Weining Lu, Stuart B Bauer, Matthias Hammerschmidt, Raimund Wagener, Friedhelm Hildebrandt
Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause (40-50%) of chronic kidney disease (CKD) in children. About 40 monogenic causes of CAKUT have so far been discovered. To date less than 20% of CAKUT cases can be explained by mutations in these 40 genes. To identify additional monogenic causes of CAKUT, we performed whole exome sequencing (WES) and homozygosity mapping (HM) in a patient with CAKUT from Indian origin and consanguineous descent. We identified a homozygous missense mutation (c...
2018: PloS One
https://www.readbyqxmd.com/read/29350405/reactive-oxygen-species-induced-parthanatos-of-immunocytes-by-human-cytomegalovirus-associated-substance
#8
Jung Heon Kim, Jiyeon Kim, Jin Roh, Chan-Sik Park, Ju-Young Seoh, Eung-Soo Hwang
Previous studies examined various immune evasion strategies of human cytomegalovirus (HCMV) to understand HCMV pathogenesis. Although the mechanism that underlies immunocyte destruction near HCMV-infected lesions has yet to be established, we show that substances produced by HCMV-infected cells induce death in several types of immunocytes, but not in fibroblasts or astrocytomas. These substances contain HCMV proteins and were termed HCMV-associated insoluble substance (HCMVAIS). We characterized this mechanism of cell death induced by HCMVAIS to understand the death of immunocytes near HCMV-infected lesions...
January 19, 2018: Microbiology and Immunology
https://www.readbyqxmd.com/read/29348827/molecular-genetic-profiling-and-high-throughput-in-vitro-drug-screening-in-nut-midline-carcinoma-an-aggressive-and-fatal-disease
#9
Anja Stirnweiss, Joyce Oommen, Rishi S Kotecha, Ursula R Kees, Alex H Beesley
NUT midline carcinoma (NMC) is a rare and aggressive cancer, with survival typically less than seven months, that can arise in people of any age. Genetically, NMC is defined by the chromosomal fusion of NUTM1 with a chromatin-binding partner, typically the bromodomain-containing protein BRD4. However, little is known about other genetic aberrations in this disease. In this study, we used a unique panel of cell lines to describe the molecular-genetic features of NMC. Next-generation sequencing identified a recurring high-impact mutation in the DNA-helicase gene RECQL5 in 75% of lines studied, and biological signals from mutation-signature and network analyses consistent with a general failure in DNA-repair...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348560/discovery-of-a-small-molecule-protein-kinase-c%C3%AE-selective-activator-with-promising-application-in-colon-cancer-therapy
#10
Cláudia Bessa, Joana Soares, Liliana Raimundo, Joana B Loureiro, Célia Gomes, Flávio Reis, Miguel L Soares, Daniel Santos, Chetna Dureja, Saumya R Chaudhuri, Cynthia Lopez-Haber, Marcelo G Kazanietz, Jorge Gonçalves, Maria F Simões, Patrícia Rijo, Lucília Saraiva
Protein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first small-molecule PKCδ-selective activator, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (Roy-Bz), which binds to the PKCδ-C1-domain. Roy-Bz potently inhibited the proliferation of colon cancer cells by inducing a PKCδ-dependent mitochondrial apoptotic pathway involving caspase-3 activation...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348472/viral-highway-to-nucleus-exposed-by-image-correlation-analyses
#11
Elina Mäntylä, Jenu V Chacko, Vesa Aho, Colin R Parrish, Victor Shahin, Michael Kann, Michelle A Digman, Enrico Gratton, Maija Vihinen-Ranta
Parvoviral genome translocation from the plasma membrane into the nucleus is a coordinated multistep process mediated by capsid proteins. We used fast confocal microscopy line scan imaging combined with image correlation methods including auto-, pair- and cross-correlation, and number and brightness analysis, to study the parvovirus entry pathway at the single-particle level in living cells. Our results show that the endosome-associated movement of virus particles fluctuates from fast to slow. Fast transit of single cytoplasmic capsids to the nuclear envelope is followed by slow movement of capsids and fast diffusion of capsid fragments in the nucleoplasm...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348368/defining-the-physiological-role-of-srp-in-protein-targeting-efficiency-and-specificity
#12
Elizabeth A Costa, Kelly Subramanian, Jodi Nunnari, Jonathan S Weissman
The signal recognition particle (SRP) enables cotranslational delivery of proteins for translocation into the endoplasmic reticulum (ER), but its full in vivo role remains incompletely explored. We combined rapid auxin-induced SRP degradation with proximity-specific ribosome profiling to define SRP's in vivo function in yeast. Despite the classic view that SRP recognizes N-terminal signal sequences, we show that SRP was generally essential for targeting transmembrane domains regardless of their position relative to the N terminus...
January 18, 2018: Science
https://www.readbyqxmd.com/read/29348317/head-to-head-comparison-of-11c-pbr28-and-18f-ge180-for-the-quantification-of-tspo-in-the-human-brain
#13
Paolo Zanotti-Fregonara, Belen Pascual, Gaia Rizzo, Meixiang Yu, Neha Pal, David Beers, Randall Carter, Stanley Appel, Nazem Atassi, Joseph Masdeu
Introduction:18F-GE180 is a third-generation positron emission tomography (PET) tracer to quantify the translocator protein TSPO, a biomarker for inflammation. The aim of this study was to compare head-to-head 18F-GE180 to the well-established translocator protein (TSPO) tracer 11C-PBR28, by scanning with either tracer during the same day in the same subjects. Materials and Methods: Five subjects underwent a 90-minute PET scan with 11C-PBR28 in the morning and 18F-GE180 in the afternoon. A metabolite-corrected arterial input function was obtained in each subject for both tracers, and the brain uptake was quantified with a two-tissue compartmental model...
January 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29348211/membrane-protein-insertion-through-a-mitochondrial-%C3%AE-barrel-gate
#14
Alexandra I C Höhr, Caroline Lindau, Christophe Wirth, Jian Qiu, David A Stroud, Stephan Kutik, Bernard Guiard, Carola Hunte, Thomas Becker, Nikolaus Pfanner, Nils Wiedemann
The biogenesis of mitochondria, chloroplasts, and Gram-negative bacteria requires the insertion of β-barrel proteins into the outer membranes. Homologous Omp85 proteins are essential for membrane insertion of β-barrel precursors. It is unknown if precursors are threaded through the Omp85-channel interior and exit laterally or if they are translocated into the membrane at the Omp85-lipid interface. We have mapped the interaction of a precursor in transit with the mitochondrial Omp85-channel Sam50 in the native membrane environment...
January 19, 2018: Science
https://www.readbyqxmd.com/read/29348018/myocardial-inflammation-predicts-remodeling-and-neuroinflammation-after-myocardial-infarction
#15
James T Thackeray, Henri C Hupe, Yong Wang, Jens P Bankstahl, Georg Berding, Tobias L Ross, Johann Bauersachs, Kai C Wollert, Frank M Bengel
BACKGROUND: The local inflammatory tissue response after acute myocardial infarction (MI) determines subsequent healing. Systemic interaction may induce neuroinflammation as a precursor to neurodegeneration. OBJECTIVES: This study sought to assess the influence of MI on cardiac and brain inflammation using noninvasive positron emission tomography (PET) of the heart-brain axis. METHODS: After coronary artery ligation or sham surgery, mice (n = 49) underwent serial whole-body PET imaging of the mitochondrial translocator protein (TSPO) as a marker of activated macrophages and microglia...
January 23, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29347788/particle-transport-across-a-channel-via-an-oscillating-potential
#16
Yizhou Tan, Jannes Gladrow, Ulrich F Keyser, Leonardo Dagdug, Stefano Pagliara
Membrane protein transporters alternate their substrate-binding sites between the extracellular and cytosolic side of the membrane according to the alternating access mechanism. Inspired by this intriguing mechanism devised by nature, we study particle transport through a channel coupled with an energy well that oscillates its position between the two entrances of the channel. We optimize particle transport across the channel by adjusting the oscillation frequency. At the optimal oscillation frequency, the translocation rate through the channel is a hundred times higher with respect to free diffusion across the channel...
November 2017: Physical Review. E
https://www.readbyqxmd.com/read/29346133/dexmedetomidine-impairs-diaphragm-function-and-increases-oxidative-stress-but-does-not-aggravate-diaphragmatic-atrophy-in-mechanically-ventilated-rats
#17
Thomas Breuer, Christian Bleilevens, Rolf Rossaint, Gernot Marx, Julian Gehrenkemper, Henning Dierksen, Antoine Delpierre, Joachim Weis, Ghislaine Gayan-Ramirez, Christian S Bruells
BACKGROUND: Anesthetics in ventilated patients are critical as any cofactor hampering diaphragmatic function may have a negative impact on the weaning progress and therefore on patients' mortality. Dexmedetomidine may display antioxidant and antiproteolytic properties, but it also reduced glucose uptake by the muscle, which may impair diaphragm force production. This study tested the hypothesis that dexmedetomidine could inhibit ventilator-induced diaphragmatic dysfunction. METHODS: Twenty-four rats were separated into three groups (n = 8/group)...
January 18, 2018: Anesthesiology
https://www.readbyqxmd.com/read/29346075/human-papillomavirus-e6-interaction-with-cellular-pdz-domain-proteins-modulates-yap-nuclear-localization
#18
Sydney Webb Strickland, Nicole Brimer, Charles Lyons, Scott B Vande Pol
HPV E6 oncoproteins associate with cellular PDZ proteins. In addition to previously identified cellular PDZ proteins, we found association of the HPV16 E6 PBM with the Dystrophin Glycoprotein Complex, LRCC1, and SLC9A3R2. HPV18 E6 had additional associations when lysates from adenomatous cell lines were used including LRPPRC, RLGAPB, EIF3A, SMC2 and 3, AMOT, AMOTL1, and ARHGEF1; some of these cellular PDZ proteins are implicated in the regulation of the YAP1 transcriptional co-activator. In keratinocytes, nuclear translocation of YAP1 was promoted by the complete HPV-16 genome, or by expression of the individual E6 or E7 oncoproteins; the activity of E6 required an intact PBM at the carboxy-terminus...
January 12, 2018: Virology
https://www.readbyqxmd.com/read/29345269/tributyltin-induces-epigenetic-changes-and-decreases-the-expression-of-nuclear-respiratory-factor-1
#19
Saki Hanaoka, Keishi Ishida, Saki Tanaka, Shuichiro Sakamoto, Katsuhiro Okuda, Seigo Sanoh, Shigeru Ohta, Yaichiro Kotake
Tributyltin (TBT), a common organotin environmental pollutant, has been widely used as a component of marine antifouling paints. We previously reported that exposure to TBT inhibits the expression and DNA binding of nuclear respiratory factor-1 (NRF-1) and causes neurotoxicity. In the present study, we focused on the epigenetic effects of TBT and investigated whether TBT decreases NRF-1 expression via epigenetic modifications in SH-SY5Y human neuroblastoma cells. First, we found that exposure to 300 nM TBT decreases NRF-1 expression...
January 18, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29344294/cardiomyocyte-restricted-low-density-lipoprotein-receptor-related-protein-6-lrp6-deletion-leads-to-lethal-dilated-cardiomyopathy-partly-through-drp1-signaling
#20
Zhidan Chen, Yang Li, Ying Wang, Juying Qian, Hong Ma, Xiang Wang, Guoliang Jiang, Ming Liu, Yanpeng An, Leilei Ma, Le Kang, Jianguo Jia, Chunjie Yang, Guoping Zhang, Ying Chen, Wei Gao, Mingqiang Fu, Zheyong Huang, Huiru Tang, Yichun Zhu, Junbo Ge, Hui Gong, Yunzeng Zou
Low density lipoprotein receptor-related protein 6 (LRP6), a wnt co-receptor, regulates multiple functions in various organs. However, the roles of LRP6 in the adult heart are not well understood. Methods: We observed LRP6 expression in heart with end-stage dilated cardiomyopathy (DCM) by western blot. Tamoxifen-inducible cardiac-specific LRP6 knockout mouse was constructed. Hemodynamic and echocardiographic analyses were performed to these mice. Results: Cardiac LRP6 expression was dramatically decreased in patients with end-stage dilated cardiomyopathy (DCM) compared to control group...
2018: Theranostics
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