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https://www.readbyqxmd.com/read/29774626/analysis-of-intra-tumor-heterogeneity-in-neurofibromatosis-type-1-plexiform-neurofibromas-and-neurofibromas-with-atypical-features-correlating-histological-and-genomic-findings
#1
Meritxell Carrió, Bernat Gel, Ernest Terribas, Adriana Carolina Zucchiatti, Teresa Moliné, Inma Rosas, Álex Teulé, Santiago Ramón Y Cajal, Juan Carlos López-Gutiérrez, Ignacio Blanco, Elisabeth Castellanos, Conxi Lázaro, Anat Stemmer-Rachamimov, Cleofé Romagosa, Eduard Serra
Plexiform neurofibromas (PNFs) are benign peripheral nerve sheath tumors involving large nerves present in 30-50% Neurofibromatosis type 1 (NF1) patients. Atypical neurofibromas (ANF) are distinct nodular lesions with atypical features on histology that arise from PNFs. The risk and timeline of malignant transformation in ANF is difficult to assess. A recent NIH workshop has stratified ANFs and separated a subgroup with multiple atypical features and higher risk of malignant transformation termed atypical neurofibromatous neoplasms with uncertain biological potential (ANNUBP)...
May 17, 2018: Human Mutation
https://www.readbyqxmd.com/read/29774232/multiple-origins-of-green-blood-in-new-guinea-lizards
#2
Zachary B Rodriguez, Susan L Perkins, Christopher C Austin
Several species of lizards from the megadiverse island of New Guinea have evolved green blood. An unusually high concentration of the green bile pigment biliverdin in the circulatory system of these lizards makes the blood, muscles, bones, tongue, and mucosal tissues bright green in color, eclipsing the crimson color from their red blood cells. This is a remarkable physiological feature because bile pigments are toxic physiological waste products of red blood cell catabolism and, when chronically elevated, cause jaundice in humans and all other vertebrates...
May 2018: Science Advances
https://www.readbyqxmd.com/read/29773658/detecting-quantifying-and-discriminating-the-mechanism-of-mosaic-chromosomal-aneuploidies-using-mad-seq
#3
Yu Kong, Esther R Berko, Anthony Marckette, Shahina B Maqbool, Claudia A Simões-Pires, David F Kronn, Qian K Ye, Masako Suzuki, Adam Auton, John Greally
Current approaches to detect and characterize mosaic chromosomal aneuploidy are limited by sensitivity, efficiency, cost or the need to culture cells. We describe the mosaic aneuploidy detection by massively-parallel sequencing (MAD-seq) capture assay and the MADSEQ analytical approach that allow low (<10%) levels of mosaicism for chromosomal aneuploidy or regional loss of heterozygosity to be detected, assigned to a meiotic or mitotic origin, and quantified as a proportion of the cells in the sample. We show results from a multi-ethnic MAD-seq (meMAD-seq) capture design that works equally well in populations of diverse racial and ethnic origins, and how the MADSEQ analytical approach can be applied to exome or whole genome sequencing data, revealing previously unrecognized aneuploidy or copy number neutral loss of heterozygosity in samples studied by the 1000 Genomes project, cell lines from public repositories, and one of the Illumina Platinum Genomes samples...
May 17, 2018: Genome Research
https://www.readbyqxmd.com/read/29771235/bordetella-pertussis-population-dynamics-and-phylogeny-in-japan-after-adoption-of-acellular-pertussis-vaccines
#4
Aldert Zomer, Nao Otsuka, Yukihiro Hiramatsu, Kazunari Kamachi, Naoko Nishimura, Takao Ozaki, Jan Poolman, Jeroen Geurtsen
Bordetella pertussis, the causative agent of whooping cough, has experienced a resurgence in the past 15 years, despite the existence of both whole-cell and acellular vaccines. Here, we performed whole genome sequencing analysis of 149 clinical strains, provided by the National Institute of Infectious Diseases (NIID), Japan, isolated in 1982-2014, after Japan became the first country to adopt acellular vaccines against B. pertussis. Additionally, we sequenced 39 strains provided by the Konan Kosei Hospital in Aichi prefecture, Japan, isolated in 2008-2013...
May 17, 2018: Microbial Genomics
https://www.readbyqxmd.com/read/29764839/lineage-restriction-analyses-in-chip-indicate-myeloid-bias-for-tet2-and-multipotent-stem-cell-origin-for-dnmt3a
#5
Manuel Buscarlet, Sylvie Provost, Yassamin Feroz Zada, Vincent Bourgoin, Luigina Mollica, Marie-Pierre Dubé, Lambert Busque
We analyzed DNA from PMN (granulocytes), CD14+ (monocytes), CD19+ (B-cells) and CD3+ (T-cells) of 107 individuals with clonal hematopoiesis of indeterminate potential (CHIP) to perform lineage restriction analysis of different gene mutations. Individuals were aged 55 to 96 (mean age: 70.0). Three lineage categories were defined: myeloid (PMN±monocytes), myelolympho-B (myeloid and B-cells), multipotent (myeloid, B and T-cells). Six individuals with aberrant patterns were excluded from analysis. Fifty-six had a single DNMT3A mutation, 24 had a single TET2 mutation, 7 had a single mutation in other genes (JAK2, ASXL1, CBL or TP53), and 14 had multiple mutations...
May 15, 2018: Blood
https://www.readbyqxmd.com/read/29764494/precision-medicine-becomes-reality-tumor-type-agnostic-therapy
#6
REVIEW
Li Yan, Wei Zhang
Precision medicine just witnessed two breakthroughs in oncology in 2017. Pembrolizumab (Keytruda), Merck's anti-programmed cell death-1 (PD-1) monoclonal antibody (mAb), received accelerated approval in May 2017 by the US Food and Drug Administration for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having microsatellite instability-high (MSI-H) or deficient DNA mismatch repair (dMMR). Shortly after, nivolumab (Opdivo), Bristol-Myers Squibb's anti-PD-1 mAb, gained an accelerated approval in August 2017 for adult and pediatric patients with MSI-H or dMMR metastatic colorectal cancer that has progressed after standard chemotherapy...
March 31, 2018: Cancer communications
https://www.readbyqxmd.com/read/29763607/biomedical-applications-of-lumazine-synthase
#7
Yangjie Wei, Prashant Kumar, Newton Wahome, Nicholas J Mantis, C Russell Middaugh
Lumazine synthase (LS) is a family of enzyme involved in the penultimate step in the biosynthesis of riboflavin. Its enzymatic mechanism has been well defined and many LS structures have been solved using x-ray crystallography or cryo-electron microscopy. LS is composed of homo-oligomers, which vary in size and subunit number, including pentamers, decamers, and icosahedral sixty-mers, depending on its species of origin. Research on LS has expanded beyond the initial focus on its enzymatic function to properties related to its oligomeric structure and exceptional conformational stability...
May 12, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29760102/broad-receptor-engagement-of-an-emerging-global-coronavirus-may-potentiate-its-diverse-cross-species-transmissibility
#8
Wentao Li, Ruben J G Hulswit, Scott P Kenney, Ivy Widjaja, Kwonil Jung, Moyasar A Alhamo, Brenda van Dieren, Frank J M van Kuppeveld, Linda J Saif, Berend-Jan Bosch
Porcine deltacoronavirus (PDCoV), identified in 2012, is a common enteropathogen of swine with worldwide distribution. The source and evolutionary history of this virus is, however, unknown. PDCoV belongs to the Deltacoronavirus genus that comprises predominantly avian CoV. Phylogenetic analysis suggests that PDCoV originated relatively recently from a host-switching event between birds and mammals. Insight into receptor engagement by PDCoV may shed light into such an exceptional phenomenon. Here we report that PDCoV employs host aminopeptidase N (APN) as an entry receptor and interacts with APN via domain B of its spike (S) protein...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29757276/fluorescence-molecular-tomography-for-in-vivo-imaging-of-glioblastoma-xenografts
#9
Jorge A Benitez, Ciro Zanca, Jianhui Ma, Webster K Cavenee, Frank B Furnari
Tumorigenicity is the capability of cancer cells to form a tumor mass. A widely used approach to determine if the cells are tumorigenic is by injecting immunodeficient mice subcutaneously with cancer cells and measuring the tumor mass after it becomes visible and palpable. Orthotopic injections of cancer cells aim to introduce the xenograft in the microenvironment that most closely resembles the tissue of origin of the tumor being studied. Brain cancer research requires intracranial injection of cancer cells to allow the tumor formation and analysis in the unique microenvironment of the brain...
April 26, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29755405/dual-paraneoplastic-endocrine-syndromes-heralding-onset-of-extrapulmonary-small-cell-carcinoma-a-case-report-and-narrative-review
#10
Jill B Feffer, Natalia M Branis, Jeanine B Albu
Objective: Extrapulmonary small cell carcinoma (EPSCC) is rare and frequent metastases at presentation can complicate efforts to identify a site of origin. In particular, SCC comprises <1% of prostate cancers and has been implicated in castration resistance. Methods: Clinical, laboratory, imaging, and pathology data are presented. Results: A 56-year-old man with locally advanced prostate adenocarcinoma on androgen deprivation therapy presented with a clogged nephrostomy tube...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29755021/a-single-center-experience-of-post-transplant-lymphoproliferative-disorder-ptld-cases-after-pediatric-liver-transplantation-incidence-outcomes-and-association-with-food-allergy
#11
Zeren Barış, Figen Özçay, Özlem Yılmaz Özbek, Nihan Haberal, Faik Sarıalioğlu, Mehmet Haberal
BACKGROUND/AIMS: We evaluated our 16-year single-center experience of pediatric post-transplant lymphoproliferative disorder (PTLD) cases who underwent liver transplantation between 2001 and 2017. MATERIALS AND METHODS: Of the 236 pediatric patients who underwent liver transplantation between 2001 and 2017, the clinical and laboratory data of eight patients diagnosed with PTLD were reviewed. The pre-transplant Epstein-Barr virus (EBV) status of 172 patients was also recorded...
May 2018: Turkish Journal of Gastroenterology: the Official Journal of Turkish Society of Gastroenterology
https://www.readbyqxmd.com/read/29752384/a-regulatory-pathway-involving-retinoic-acid-and-calcineurin-demarcates-and-maintains-joint-cells-and-osteoblasts-in-the-fin-regenerate
#12
Stephanie C McMillan, Jing Zhang, Hue-Eileen Phan, Shirine Jeradi, Leona Probst, Matthias Hammerschmidt, Marie-Andrée Akimenko
During zebrafish fin regeneration, blastema cells lining the epidermis differentiate into osteoblasts and joint cells to reconstruct the segmented bony rays. We show that osteoblasts and joint cells originate from a common cell lineage, but are committed to different cell fates. Pre-osteoblasts expressing runx2a/b commit to the osteoblast lineage upon expressing sp7 , while the strong upregulation of hoxa13a correlates with a commitment to a joint cell type. In the distal regenerate, hoxa13a , evx1, and pthlha are sequentially upregulated at regular intervals to define the newly identified presumptive joint cells...
May 11, 2018: Development
https://www.readbyqxmd.com/read/29750989/altered-ca-2-signaling-in-enamelopathies
#13
REVIEW
Miriam Eckstein, Francisco J Aulestia, Meerim K Nurbaeva, Rodrigo S Lacruz
Biomineralization requires the controlled movement of ions across cell barriers to reach the sites of crystal growth. Mineral precipitation occurs in aqueous phases as fluids become supersaturated with specific ionic compositions. In the biological world, biomineralization is dominated by the presence of calcium (Ca2+ ) in crystal lattices. Ca2+ channels are intrinsic modulators of this process, facilitating the availability of Ca2+ within cells in a tightly regulated manner in time and space. Unequivocally, the most mineralized tissue produced by vertebrates, past and present, is dental enamel...
May 8, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29750582/a-cytotoxic-three-dimensional-spheroid-high-throughput-assay-using-patient-derived-glioma-stem-cells
#14
Victor Quereda, Shurong Hou, Franck Madoux, Louis Scampavia, Timothy P Spicer, Derek Duckett
Glioblastoma (GBM) is the most aggressive primary brain cancer with an average survival time after diagnosis of only 12-14 months, with few (<5%) long-term survivors. A growing body of work suggests that GBMs contain a small population of glioma stem cells (GSCs) that are thought to be major contributors to treatment resistance and disease relapse. Identifying compounds that modulate GSC proliferation would provide highly valuable molecular probes of GSC-directed signaling. However, targeting GSCs pharmacologically has been challenging...
May 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29750167/prognostic-significance-of-blood-transfusion-in-elderly-patients-with-primary-diffuse-large-b-cell-lymphoma
#15
Liping Fan, Danhui Fu, Jinquan Hong, Haobo Huang, Wenqian He, Feng Zeng, Qiuyan Lin, Qianling Xie
The current study sought to evaluate whether blood transfusions affect survival of elderly patients with primary diffuse large B-cell lymphoma (DLBCL). A total of 104 patients aged 60 years and over were enrolled and divided into two groups: 24 patients who received transfusions and 80 patients who did not. Statistical analyses showed significant differences in LDH levels, platelet (Plt) counts, and hemoglobin (Hb) and albumin (Alb) levels between the two groups. Univariate analyses showed that LDH level ≥ 245 IU/L, cell of origin (germinal center/nongerminal center), and blood transfusion were associated with both overall survival (OS) and progression-free survival (PFS)...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29746690/retrospective-analysis-reproducibility-of-interblastomere-differences-of-mrna-expression-in-2-cell-stage-mouse-embryos-is-remarkably-poor-due-to-combinatorial-mechanisms-of-blastomere-diversification
#16
E Casser, S Israel, S Schlatt, V Nordhoff, M Boiani
STUDY QUESTION: What is the prevalence, reproducibility and biological significance of transcriptomic differences between sister blastomeres of the mouse 2-cell embryo? SUMMARY ANSWER: Sister 2-cell stage blastomeres are distinguishable from each other by mRNA analysis, attesting to the fact that differentiation starts mostly early in the mouse embryo; however, the interblastomere differences are poorly reproducible and invoke the combinatorial effects of known and new mechanisms of blastomere diversification...
May 9, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29746265/microenvironment-signaling-driving-lymphomagenesis
#17
Léa Verdière, Frédéric Mourcin, Karin Tarte
PURPOSE OF REVIEW: In addition to the recent progresses in the description of the genetic landscape of B-cell non-Hodgkin's lymphomas, tumor microenvironment has progressively emerged as a central determinant of early lymphomagenesis, subclonal evolution, drug resistance, and late progression/transformation. The purpose of this review is to outline the most recent findings regarding malignant B-cell niche composition and organization supporting direct and indirect tumor-promoting functions of lymphoma microenvironment...
May 8, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29745271/fetal-hemoglobin-in-the-maternal-circulation-contribution-of-fetal-red-blood-cells
#18
Mutaz Dana, Eitan Fibach
The major hemoglobin (Hb) during fetal life is fetal Hb (Hb F). It is mostly replaced by adult Hbs before birth and during the first year of life. In adults, where Hb F comprises <2.0% of the total Hb, it is not homogenously distributed among the red blood cells (RBCs) but is concentrated in a few RBCs, termed F-cells. Interestingly, for reasons that are unclear, Hb F increases in the maternal circulation during pregnancy. This increased Hb F could have two potential origins that are not mutually exclusive: A) maternal origin, due to inducing environment of Hb F in the maternal erythroid precursors; B) fetal origin, due to fetal cells crossing the placenta and entering the maternal circulation...
May 10, 2018: Hemoglobin
https://www.readbyqxmd.com/read/29743966/changes-of-keap1-nrf2-and-ikb-nf-%C3%AE%C2%BA-b-expression-levels-induced-by-cell-free-dna-in-different-cell-types
#19
Svetlana V Kostyuk, Lev N Porokhovnik, Elizaveta S Ershova, Elena M Malinovskaya, Marina S Konkova, Larisa V Kameneva, Olga A Dolgikh, Vladimir P Veiko, Vladimir M Pisarev, Andrew V Martynov, Vasilina A Sergeeva, Andrew A Kaliyanov, Anton D Filev, Julia M Chudakova, Margarita S Abramova, Serguey I Kutsev, Vera L Izhevskaya, Nataliya N Veiko
Cell-free DNA (cfDNA) is a circulating DNA of nuclear and mitochondrial origin mainly derived from dying cells. Recent studies have shown that cfDNA is a stress signaling DAMP (damage-associated molecular pattern) molecule. We report here that the expression profiles of cfDNA-induced factors NRF2 and NF- κ B are distinct depending on the target cell's type and the GC-content and oxidation rate of the cfDNA. Stem cells (MSC) have shown higher expression of NRF2 without inflammation in response to cfDNA. In contrast, inflammatory response launched by NF- κ B was dominant in differentiated cells HUVEC, MCF7, and fibroblasts, with a possibility of transition to massive apoptosis...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29743361/a-novel-strategy-to-adapt-shiv-e1-carrying-env-from-an-rv144-volunteer-to-rhesus-macaques-coreceptor-switch-and-final-recovery-of-a-pathogenic-virus-with-exclusive-r5-tropism
#20
Hanna B Scinto, Sandeep Gupta, Swati Thorat, Muhammad M Mukhtar, Anthony Griffiths, Jennifer Delgado, Elizabeth Plake, Hemant K Vyas, Amanda Strickland, Siddappa N Byrareddy, David C Montefiori, Celia LaBranche, Ranajit Pal, Jim Treece, Sharon Orndorff, Maria Grazia Ferrari, Deborah Weiss, Agnes-Laurence Chenine, Robert McLinden, Nelson Michael, Jerome H Kim, Merlin Robb, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Ruth M Ruprecht
The Phase III RV144 HIV vaccine trial conducted in Thailand remains the only study to show efficacy in decreasing HIV acquisition risk. In Thailand, circulating recombinant forms of HIV clades A/E (CRF01_AE) predominate; in such viruses, env originates from clade E (HIV-E). We constructed a simian-human immunodeficiency virus (SHIV) chimera carrying env isolated from an RV144 placebo recipient in the SHIV-1157ipd3N4 backbone. The latter contains long terminal repeats (LTRs) with duplicated NF-κB sites, thus resembling HIV LTRs...
May 9, 2018: Journal of Virology
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