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https://www.readbyqxmd.com/read/28437540/characterization-of-gene-expression-phenotype-in-amyotrophic-lateral-sclerosis-monocytes
#1
Weihua Zhao, David R Beers, Kristopher G Hooten, Douglas H Sieglaff, Aijun Zhang, Shanker Kalyana-Sundaram, Christopher M Traini, Wendy S Halsey, Ashley M Hughes, Ganesh M Sathe, George P Livi, Guo-Huang Fan, Stanley H Appel
Importance: Amyotrophic lateral sclerosis (ALS) is a common adult-onset neurodegenerative disease characterized by selective loss of upper and lower motor neurons. Patients with ALS have persistent peripheral and central inflammatory responses including abnormally functioning T cells and activated microglia. However, much less is known about the inflammatory gene profile of circulating innate immune monocytes in these patients. Objective: To characterize the transcriptomics of peripheral monocytes in patients with ALS...
April 24, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28437524/the-evolution-of-the-plateau-an-optical-coherence-tomography-signature-seen-in-geographic-atrophy
#2
Anna C S Tan, Polina Astroz, Kunal K Dansingani, Jason S Slakter, Lawrence A Yannuzzi, Christine A Curcio, K Bailey Freund
Purpose: Histologic details of progression routes to geographic atrophy (GA) in AMD are becoming available through optical coherence tomography (OCT). We studied the origins and evolution of an OCT signature called plateau in eyes with GA and suggested a histologic correlate. Methods: Serial eye-tracked OCT scans and multimodal imaging were acquired from eight eyes of seven patients with GA and plateau signatures over a mean follow-up of 7.7 years (range, 3.7-11...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28437275/descemet-membrane-endothelial-keratoplasty-after-failed-descemet-stripping-without-endothelial-keratoplasty
#3
Rohini Rao, Durga S Borkar, Kathryn A Colby, Peter B Veldman
PURPOSE: To describe the clinical course, surgical experience, and postoperative outcomes of 3 patients with Fuchs endothelial dystrophy who underwent Descemet membrane endothelial keratoplasty (DMEK) after failed Descemet stripping without endothelial keratoplasty. METHODS: Three patients who underwent DMEK for management of persistent corneal edema after deliberate Descemet stripping in the setting of Fuchs endothelial dystrophy were identified. Patients were examined at day 1, week 1, and months 1, 3, and 6 after DMEK...
April 21, 2017: Cornea
https://www.readbyqxmd.com/read/28436602/accuracy-of-circulating-histones-in-predicting-persistent-organ-failure-and-mortality-in-patients-with-acute-pancreatitis
#4
T Liu, W Huang, P Szatmary, S T Abrams, Y Alhamdi, Z Lin, W Greenhalf, G Wang, R Sutton, C H Toh
BACKGROUND: Early prediction of acute pancreatitis severity remains a challenge. Circulating levels of histones are raised early in mouse models and correlate with disease severity. It was hypothesized that circulating histones predict persistent organ failure in patients with acute pancreatitis. METHODS: Consecutive patients with acute pancreatitis fulfilling inclusion criteria admitted to Royal Liverpool University Hospital were enrolled prospectively between June 2010 and March 2014...
April 24, 2017: British Journal of Surgery
https://www.readbyqxmd.com/read/28436392/the-dna-damage-response-in-neurons-die-by-apoptosis-or-survive-in-a-senescence-like-state
#5
Edward Fielder, Thomas von Zglinicki, Diana Jurk
Neurons are exposed to high levels of DNA damage from both physiological and pathological sources. Neurons are post-mitotic and their loss cannot be easily recovered from; to cope with DNA damage a complex pathway called the DNA damage response (DDR) has evolved. This recognizes the damage, and through kinases such as ataxia-telangiectasia mutated (ATM) recruits and activates downstream factors that mediate either apoptosis or survival. This choice between these opposing outcomes integrates many inputs primarily through a number of key cross-road proteins, including ATM, p53, and p21...
April 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28435765/chronic-nephropathy-from-dietary-hyperoxaluria-sustained-improvement-of-renal-function-after-dietary-intervention
#6
Yijuan Sun, Bruce L Horowitz, Karen S Servilla, Joanna R Fair, Darlene Vigil, Kavitha Ganta, Larry Massie, Antonios H Tzamaloukas
A 56-year-old man with stable chronic kidney disease (CKD) for two years following a single episode of calcium oxalate urolithiasis developed progressive elevation of his serum creatinine concentration. Urinalysis revealed pyuria and white cell casts, a few red blood cells, minimal proteinuria, and no crystals. Urine culture was sterile. Gallium scintigraphy was consistent with interstitial nephritis. Proton pump inhibitor intake was discontinued, and a short course of oral corticosteroids was initiated. Percutaneous kidney biopsy, performed because of the continued deterioration of renal function to a minimum estimated glomerular filtration rate (eGFR) value of 15 mL/min per 1...
March 20, 2017: Curēus
https://www.readbyqxmd.com/read/28435452/the-yap1-six2-axis-is-required-for-ddx3-mediated-tumor-aggressiveness-and-cetuximab-resistance-in-kras-wild-type-colorectal-cancer
#7
De-Wei Wu, Po-Lin Lin, Lee Wang, Chi-Chou Huang, Huei Lee
The mechanism underlying tumor aggressiveness and cetuximab (CTX) resistance in KRAS-wild-type (KRAS -WT) colorectal cancer remains obscure. We here provide evidence that DDX3 promoted soft agar growth and invasiveness of KRAS-WT cells, as already confirmed in KRAS-mutated cells. Mechanistically, increased KRAS expression induced ROS production, which elevated HIF-1α and YAP1 expression. Increased HIF-1α persistently promoted DDX3 expression via a KRAS/ROS/HIF-1α feedback loop. DDX3-mediated aggressiveness and CTX resistance were regulated by the YAP1/SIX2 axis in KRAS-WT cells and further confirmed in animal models...
2017: Theranostics
https://www.readbyqxmd.com/read/28435138/proteomic-analysis-of-a-mosquito-host-cell-response-to-persistent-wolbachia-infection
#8
Gerald Baldridge, LeeAnn Higgins, Bruce Witthuhn, Todd Markowski, Abigail Baldridge, Anibal Armien, Ann Fallon
Wolbachia pipientis, an obligate intracellular bacterium associated with arthropods and filarial worms, is a target for filarial disease treatment and provides a gene drive agent for insect vector population suppression/replacement. We compared proteomes of Aedes albopictus mosquito C/wStr1 cells persistently infected with Wolbachia strain wStr, relative to uninfected C7-10 control cells. Among approximately 2,500 proteins, iTRAQ data identified 815 differentially abundant proteins. As functional classes, energy and central intermediary metabolism proteins were elevated in infected cells, while suppressed proteins with roles in host DNA replication, transcription and translation suggested that Wolbachia suppresses pathways that support host cell growth and proliferation...
April 20, 2017: Research in Microbiology
https://www.readbyqxmd.com/read/28434229/the-cell-cycle-dependent-kinase-cdk9-is-a-post-exposure-drug-target-against-human-adenoviruses
#9
Vibhu Prasad, Maarit Suomalainen, Silvio Hemmi, Urs F Greber
Human adenoviruses (HAdVs) infect respiratory, gastrointestinal and urinary tracts, and give rise to eye infections and epidemic keratoconjunctivitis (EKC). They persist in lymphoid tissue, and cause morbidity and mortality in immunocompromised people. Treatments with significant post-exposure efficacy are not available. Here, we report that inhibition of the cell cycle-dependent kinase 9 (Cdk9) by RNA-interference, or the compound Flavopiridol blocked infections with HAdV-C2/5, EKC-causing HAdV-D8/37, and progeny formation in human corneal epithelial and cancer cells...
April 24, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28434147/increasing-the-safety-and-efficacy-of-chimeric-antigen-receptor-t-cell-therapy
#10
REVIEW
Hua Li, Yangbing Zhao
Chimeric antigen receptor (CAR) T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or "on-target/off-tumor" toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strategies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vector designs to increase both the safety and efficacy, further T cell modification to overcome the tumor-associated immune suppression, and using gene editing technologies to generate universal CAR T cells...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28434126/relapse-of-nephrotic-syndrome-during-post-rituximab-peripheral-blood-b-lymphocyte-depletion
#11
Mai Sato, Koichi Kamei, Masao Ogura, Kenji Ishikura, Shuichi Ito
BACKGROUND: Rituximab is effective against complicated childhood steroid-dependent nephrotic syndrome (SDNS). Peripheral blood B-lymphocyte (B-cell) depletion is strongly correlated with persistent remission, relapse rarely occurring during B-cell depletion; however, we have encountered several such patients. METHODS: We retrospectively analyzed the characteristics and clinical course of 82 patients with SDNS treated with rituximab from January 2007 to December 2012 in our institution...
April 22, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28433936/sustained-viral-gene-delivery-from-a-micro-fibrous-elastomeric-cardiac-patch-to-the-ischemic-rat-heart
#12
Xinzhu Gu, Yasumoto Matsumura, Ying Tang, Souvik Roy, Richard Hoff, Bing Wang, William R Wagner
Biodegradable and elastomeric patches have been applied to the surface of infarcted hearts as temporary mechanical supports to effectively alter adverse left ventricular remodeling processes. In this report, recombinant adeno-associated virus (AAV), known for its persistent transgene expression and low pathogenicity, was incorporated into elastomeric polyester urethane urea (PEUU) and polyester ether urethane urea (PEEUU) and processed by electrospinning into two formats (solid fibers and core-sheath fibers) designed to influence the controlled release behavior...
April 14, 2017: Biomaterials
https://www.readbyqxmd.com/read/28433662/iron-and-thiol-redox-signaling-in-cancer-an-exquisite-balance-to-escape-ferroptosis
#13
REVIEW
Shinya Toyokuni, Fumiya Ito, Kyoko Yamashita, Yasumasa Okazaki, Shinya Akatsuka
Epidemiological data indicate a constant worldwide increase in cancer mortality, although the age of onset is increasing. Recent accumulation of genomic data on human cancer via next-generation sequencing confirmed that cancer is a disease of genome alteration. In many cancers, the Nrf2 transcription system is activated via mutations either in Nrf2 or Keap1 ubiquitin ligase, leading to persistent activation of the genes with antioxidative functions. Furthermore, deep sequencing of passenger mutations is clarifying responsible cancer causative agent(s) in each case, including aging, APOBEC activation, smoking and UV...
April 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28433419/disconnect-between-alcohol-induced-alterations-in-chromatin-structure-and-gene-transcription-in-a-mouse-embryonic-stem-cell-model-of-exposure
#14
Kylee J Veazey, Haiqing Wang, Yudhishtar S Bedi, William M Skiles, Richard Cheng-An Chang, Michael C Golding
Alterations to chromatin structure induced by environmental insults have become an attractive explanation for the persistence of exposure effects into subsequent life stages. However, a growing body of work examining the epigenetic impact that alcohol and other drugs of abuse exert consistently notes a disconnection between induced changes in chromatin structure and patterns of gene transcription. Thus, an important question is whether perturbations in the 'histone code' induced by prenatal exposures to alcohol implicitly subvert gene expression, or whether the hierarchy of cellular signaling networks driving development is such that they retain control over the transcriptional program...
January 11, 2017: Alcohol
https://www.readbyqxmd.com/read/28432926/tick-borne-encephalitis-virus-infects-human-brain-microvascular-endothelial-cells-without-compromising-blood-brain-barrier-integrity
#15
Martin Palus, Marie Vancova, Jana Sirmarova, Jana Elsterova, Jan Perner, Daniel Ruzek
Alteration of the blood-brain barrier (BBB) is a hallmark of tick-borne encephalitis (TBE), a life-threating human viral neuroinfection. However, the mechanism of BBB breakdown during TBE, as well as TBE virus (TBEV) entry into the brain is unclear. Here, primary human microvascular endothelial cells (HBMECs) were infected with TBEV to study interactions with the BBB. Although the number of infected cells was relatively low in culture (<5%), the infection was persistent with high TBEV yields (>10(6)pfu/ml)...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28432399/-when-is-surgical-resection-of-metastases-in-testicular-germ-cell-tumors-indicated-and-is-there-a-scientific-basis
#16
A Heidenreich, P Paffenholz, F Haidl, D Pfister
Surgical resection of metastases represents an integral part of curative management in patients with testicular germ cell tumors (GCT). Primary nerve-sparing retroperitoneal lymph node dissection (nsRPLND) for low volume metastases in clinical stages I-IIB has to be differentiated from the more complex and more extensive postchemotherapeutic procedures. In Europe, primary nerve-sparing retroperitoneal lymph node dissection (nsRPLND) for clinical stage I nonseminomatous GCT (NSGCT) plays a subordinate. In clinical stage IIA/B, nsRPLND is indicated for patients with marker-negative metastases in whom cure rates of about 65% can be achieved with surgery alone...
April 21, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28432353/severe-hearing-loss-and-outer-hair-cell-death-in-homozygous-foxo3-knockout-mice-after-moderate-noise-exposure
#17
Felicia Gilels, Stephen T Paquette, Holly J Beaulac, Anwen Bullen, Patricia M White
Noise induced hearing loss (NIHL) is a disease that affects millions of Americans. Identifying genetic pathways that influence recovery from noise exposure is an important step forward in understanding NIHL. The transcription factor Foxo3 integrates the cellular response to oxidative stress and plays a role in extending lifespan in many organisms, including humans. Here we show that Foxo3 is required for auditory function after noise exposure in a mouse model system, measured by ABR. Absent Foxo3, outer hair cells are lost throughout the middle and higher frequencies...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432120/two-glycosaminoglycan-binding-domains-of-the-mouse-cytomegalovirus-encoded-chemokine-mck-2-are-critical-for-oligomerization-of-the-full-length-protein
#18
Sergio M Pontejo, Philip M Murphy
Chemokines are essential for antimicrobial host defenses and tissue repair. Herpesviruses and poxviruses also encode chemokines, copied from their hosts and repurposed for multiple functions, including immune evasion. The CC chemokine MCK-2 encoded by mouse cytomegalovirus (MCMV) has an atypical structure consisting of a classic chemokine domain N-terminal to a second unique domain, resulting from the splicing of MCMV ORFs m131 and m129. MCK-2 is essential for full MCMV infectivity in macrophages and for persistent infection in the salivary gland...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28431961/ionizing-radiation-induces-long-term-senescence-in-endothelial-cells-through-mitochondrial-respiratory-complex-ii-dysfunction-and-superoxide-generation
#19
Audrey Lafargue, Charlotte Degorre, Isabelle Corre, Marie-Clotilde Alves-Guerra, Marie-Hélène Gaugler, François Vallette, Claire Pecqueur, François Paris
Ionizing radiation causes oxidative stress, leading to acute and late cellular responses. We previously demonstrated that irradiation of non-proliferating endothelial cells, as observed in normal tissues, induces early apoptosis, which can be inhibited by pretreatment with Sphingosine-1-Phosphate. We now propose to better characterize the long-term radiation response of endothelial cells by studying the molecular pathways associated with senescence and its link with acute apoptosis. First, senescence was validated in irradiated quiescent microvascular HMVEC-L in a dose- and time-dependent manner by SA β-galactosidase staining, p16(Ink4a) and p21(Waf1) expression, pro-inflammatory IL-8 secretion and DNA damage response activation...
April 18, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28431398/decreased-calpain-activity-in-chronic-myeloid-leukemia-impairs-apoptosis-by-increasing-survivin-in-myeloid-progenitors-and-xiap1-in-differentiating-granulocytes
#20
Weiqi Huang, Ling Bei, Elizabeth E Hjort, Elizabeth A Eklund
Chronic Myeloid Leukemia (CML) is characterized by translocations between chromosomes 9 and 22, resulting in expression of Bcr-abl oncogenes. Although the clinical course of CML was revolutionized by development of Bcr-abl-directed tyrosine kinase inhibitors (TKIs), CML is not cured by these agents. Specifically, the majority of subjects relapsed in clinical trials attempting TKI discontinuation, suggesting persistence of leukemia stem cells (LSCs) even in molecular remission. Identifying mechanisms of CML-LSC persistence may suggest rationale therapeutic targets to augment TKI efficacy and lead to cure...
April 6, 2017: Oncotarget
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