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https://www.readbyqxmd.com/read/28340323/a-key-to-the-backdoor-into-the-castle-the-clinical-ramifications-of-immunoediting-driven-by-antigenic-competition
#1
M G Hanna, Jason David Howard
Over the last decade the field of cancer biology has gained considerable data on genomic heterogeneity. This situation creates challenges and possibly opportunities for cancer treatment. The evolution of the tumor at all stages also requires the growing malignancy to confront and avoid the immune system. What we describe here is the interaction of two immune phenomena that work together to change the characteristics of the tumor, i.e., antigenic competition and immune editing. These two systems are mutually functional and their interaction is capable of altering the characteristics of the tumor for protection and survival in an immune competent host as well as restricting the diversity of the tumor clones...
March 24, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28340168/young-children-s-acute-stress-after-a-burn-injury-disentangling-the-role-of-injury-severity-and-parental-acute-stress
#2
Ann-Christin Haag, Markus A Landolt
 Although injury severity and parental stress are strong predictors of posttraumatic adjustment in young children after burns, little is known about the interplay of these variables. This study aimed at clarifying mediation processes between injury severity and mother's, father's, and young child's acute stress.   Structural equation modeling was used to examine the relationships between injury severity and parental and child acute stress. Parents of 138 burn-injured children (ages 1-4 years) completed standardized questionnaires on average 19 days postinjury...
March 18, 2017: Journal of Pediatric Psychology
https://www.readbyqxmd.com/read/28340122/potential-role-of-patients-cyp3a-status-in-clozapine-pharmacokinetics
#3
Katalin Tóth, Gábor Csukly, Dávid Sirok, Ales Belic, Ádám Kiss, Edit Háfra, Máté Déri, Ádám Menus, István Bitter, Katalin Monostory
Background: The atypical antipsychotic clozapine is effective in treatment-resistant schizophrenia; however, the success or failure of clozapine therapy is substantially affected by the variables that impact the clozapine blood concentration. Thus, elucidating the inter-individual differences in clozapine pharmacokinetics can facilitate the personalized therapy. Methods: Since potential role in clozapine metabolism is assigned to CYP1A2, CYP2C19, CYP2D6 and CYP3A enzymes, the association between the patients' CYP-status (CYP genotypes, CYP expression) and clozapine clearance was evaluated in 92 psychiatric patients...
March 18, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28339775/mining-non-lattice-subgraphs-for-detecting-missing-hierarchical-relations-and-concepts-in-snomed-ct
#4
Licong Cui, Wei Zhu, Shiqiang Tao, James T Case, Olivier Bodenreider, Guo-Qiang Zhang
Objective: Quality assurance of large ontological systems such as SNOMED CT is an indispensable part of the terminology management lifecycle. We introduce a hybrid structural-lexical method for scalable and systematic discovery of missing hierarchical relations and concepts in SNOMED CT. Material and Methods: All non-lattice subgraphs (the structural part) in SNOMED CT are exhaustively extracted using a scalable MapReduce algorithm. Four lexical patterns (the lexical part) are identified among the extracted non-lattice subgraphs...
February 19, 2017: Journal of the American Medical Informatics Association: JAMIA
https://www.readbyqxmd.com/read/28339678/ddx4-egfp-transgenic-rat-model-for-the-study-of-germline-development-and-spermatogenesis%C3%A2
#5
Kathrin Gassei, Yi Sheng, Adetunji Fayomi, Payal Mital, Meena Sukhwani, Chih-Cheng Lin, Karen A Peters, Andrew Althouse, Hanna Valli, Kyle E Orwig
Spermatogonial stem cells (SSC) are essential for spermatogenesis and male fertility. In addition, these adult tissue stem cells can be used as vehicles for germline modification in animal models and may have application for treating male infertility. To facilitate the investigation of SSCs and germ lineage development in rats, we generated a DEAD-box helicase 4 (DDX4) (VASA) promoter-enhanced green fluorescent protein (EGFP) reporter transgenic rat. Quantitative real-time polymerase chain reaction and immunofluorescence confirmed that EGFP was expressed in the germ cells of the ovaries and testes and was absent in somatic cells and tissues...
February 20, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28339607/gross-motor-trajectories-during-the-first-year-of-life-for-preterm-infants-with-very-low-birth-weight
#6
Yu-Han Su, Suh-Fang Jeng, Wu-Shiun Hsieh, Yu-Kang Tu, Yen-Tzu Wu, Li-Chiou Chen
Background.: Early identification of motor dysfunction in very-low-birth-weight (VLBW) preterm infants is important in order to provide early intervention. Objective.: This study was to examine the motor trajectories of VLBW preterm infants during their first year of life and to investigate the predictive ability and influencing factors of the trajectories. Design and Methods.: A total of 342 VLBW preterm infants were prospectively assessed for motor development by the Alberta Infant Motor Scales at 4, 6, 9 and 12 months and for developmental outcomes using the Bayley Scales of Infant and Toddler Development- second edition at 24 months...
February 4, 2017: Physical Therapy
https://www.readbyqxmd.com/read/28339482/a-genome-wide-identification-and-analysis-of-the-dyw-deaminase-genes-in-the-pentatricopeptide-repeat-gene-family-in-cotton-gossypium-spp
#7
Bingbing Zhang, Guoyuan Liu, Xue Li, Liping Guo, Xuexian Zhang, Tingxiang Qi, Hailin Wang, Huini Tang, Xiuqin Qiao, Jinfa Zhang, Chaozhu Xing, Jianyong Wu
The RNA editing occurring in plant organellar genomes mainly involves the change of cytidine to uridine. This process involves a deamination reaction, with cytidine deaminase as the catalyst. Pentatricopeptide repeat (PPR) proteins with a C-terminal DYW domain are reportedly associated with cytidine deamination, similar to members of the deaminase superfamily. PPR genes are involved in many cellular functions and biological processes including fertility restoration to cytoplasmic male sterility (CMS) in plants...
2017: PloS One
https://www.readbyqxmd.com/read/28335082/reporting-of-mitotic-rate-in-cutaneous-melanoma-a-study-using-the-national-cancer-data-base
#8
Patrick D Lorimer, Emily C Benham, Kendall Walsh, Yimei Han, Meghan R Forster, Terry Sarantou, Richard L White, Joshua S Hill
BACKGROUND: The seventh edition of the American Joint Commission on Cancer staging manual (AJCC7, published 2009), updated thin cutaneous melanoma staging protocols with the incorporation of mitotic rate (MR). In these patients, higher MR is associated with decreased survival. This study utilizes the National Cancer Data Base (NCDB) to evaluate MR reporting since AJCC7. METHODS: The NCDB was queried for patients with primary cutaneous melanoma from 1998 to 2013...
March 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28335044/semi-automated-de-identification-of-german-content-sensitive-reports-for-big-data-analytics
#9
Hannes Seuss, Peter Dankerl, Matthias Ihle, Andrea Grandjean, Rebecca Hammon, Nicola Kaestle, Peter A Fasching, Christian Maier, Jan Christoph, Martin Sedlmayr, Alexander Cavallaro, Matthias Hammon
Purpose Projects involving collaborations between different institutions require data security via selective de-identification of words or phrases. A semi-automated de-identification tool was developed and evaluated on different types of medical reports natively and after adapting the algorithm to the text structure. Materials and Methods A semi-automated de-identification tool was developed and evaluated for its sensitivity and specificity in detecting sensitive content in written reports. Data from 4671 pathology reports (4105 + 566 in two different formats), 2804 medical reports, 1008 operation reports, and 6223 radiology reports of 1167 patients suffering from breast cancer were de-identified...
March 23, 2017: RöFo: Fortschritte Auf Dem Gebiete der Röntgenstrahlen und der Nuklearmedizin
https://www.readbyqxmd.com/read/28335032/allele-specific-ablation-rescues-electrophysiological-abnormalities-in-a-human-ips-cell-model-of-long-qt-syndrome-with-a-calm2-mutation
#10
Yuta Yamamoto, Takeru Makiyama, Takeshi Harita, Kenichi Sasaki, Yimin Wuriyanghai, Mamoru Hayano, Suguru Nishiuchi, Hirohiko Kohjitani, Sayako Hirose, Jiarong Chen, Fumika Yokoi, Taisuke Ishikawa, Seiko Ohno, Kazuhisa Chonabayashi, Hideki Motomura, Yoshinori Yoshida, Minoru Horie, Naomasa Makita, Takeshi Kimura
Background: Calmodulin is a ubiquitous Ca 2+ sensor molecule encoded by three distinct calmodulin genes, CALM1-3 . Recently, mutations in CALM1-3 have been reported to be associated with severe early-onset long-QT syndrome (LQTS). However, the underlying mechanism through which heterozygous calmodulin mutations lead to severe LQTS remains unknown, particularly in human cardiomyocytes. Objectives: We aimed to establish an LQTS disease model associated with a CALM2 mutation (LQT15) using human induced pluripotent stem cells (hiPSCs) and to assess mutant allele-specific ablation by genome editing for the treatment of LQT15...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28335020/znhit3-is-defective-in-peho-syndrome-a-severe-encephalopathy-with-cerebellar-granule-neuron-loss
#11
Anna-Kaisa Anttonen, Anni Laari, Maria Kousi, Yawei J Yang, Tiina Jääskeläinen, Mirja Somer, Eija Siintola, Eveliina Jakkula, Mikko Muona, Saara Tegelberg, Tuula Lönnqvist, Helena Pihko, Leena Valanne, Anders Paetau, Melody P Lun, Johanna Hästbacka, Outi Kopra, Tarja Joensuu, Nicholas Katsanis, Maria K Lehtinen, Jorma J Palvimo, Anna-Elina Lehesjoki
Progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an early childhood onset, severe autosomal recessive encephalopathy characterized by extreme cerebellar atrophy due to almost total granule neuron loss. By combining homozygosity mapping in Finnish families with Sanger sequencing of positional candidate genes and with exome sequencing a homozygous missense substitution of leucine for serine at codon 31 in ZNHIT3 was identified as the primary cause of PEHO syndrome. ZNHIT3 encodes a nuclear zinc finger protein previously implicated in transcriptional regulation and in small nucleolar ribonucleoprotein particle assembly and thus possibly to pre-ribosomal RNA processing...
March 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334928/functional-assessment-of-ctcf-sites-at-cytokine-sensing-mammary-enhancers-using-crispr-cas9-gene-editing-in-mice
#12
Hye Kyung Lee, Michaela Willi, Chaochen Wang, Chul Min Yang, Harold E Smith, Chengyu Liu, Lothar Hennighausen
The zinc finger protein CTCF has been invoked in establishing boundaries between genes, thereby controlling spatial and temporal enhancer activities. However, there is limited genetic evidence to support the concept that these boundaries restrict the search space of enhancers. We have addressed this question in the casein locus containing five mammary and two non-mammary genes under the control of at least seven putative enhancers. We have identified two CTCF binding sites flanking the locus and two associated with a super-enhancer...
March 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334821/in-vivo-cleavage-specificity-of-trypanosoma-brucei-editosome-endonucleases
#13
Jason Carnes, Suzanne McDermott, Atashi Anupama, Brian G Oliver, D Noah Sather, Kenneth Stuart
RNA editing is an essential post-transcriptional process that creates functional mitochondrial mRNAs in Kinetoplastids. Multiprotein editosomes catalyze pre-mRNA cleavage, uridine (U) insertion or deletion, and ligation as specified by guide RNAs. Three functionally and compositionally distinct editosomes differ by the mutually exclusive presence of the KREN1, KREN2 or KREN3 endonuclease and their associated partner proteins. Because endonuclease cleavage is a likely point of regulation for RNA editing, we elucidated endonuclease specificity in vivo...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334779/targeted-gene-knock-in-by-homology-directed-genome-editing-using-cas9-ribonucleoprotein-and-aav-donor-delivery
#14
Thomas Gaj, Brett T Staahl, Gonçalo M C Rodrigues, Prajit Limsirichai, Freja K Ekman, Jennifer A Doudna, David V Schaffer
Realizing the full potential of genome editing requires the development of efficient and broadly applicable methods for delivering programmable nucleases and donor templates for homology-directed repair (HDR). The RNA-guided Cas9 endonuclease can be introduced into cells as a purified protein in complex with a single guide RNA (sgRNA). Such ribonucleoproteins (RNPs) can facilitate the high-fidelity introduction of single-base substitutions via HDR following co-delivery with a single-stranded DNA oligonucleotide...
March 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334759/highly-efficient-biallelic-genome-editing-of-human-es-ips-cells-using-a-crispr-cas9-or-talen-system
#15
Kazuo Takayama, Keisuke Igai, Yasuko Hagihara, Rina Hashimoto, Morifumi Hanawa, Tetsushi Sakuma, Masashi Tachibana, Fuminori Sakurai, Takashi Yamamoto, Hiroyuki Mizuguchi
Genome editing research of human ES/iPS cells has been accelerated by clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) and transcription activator-like effector nucleases (TALEN) technologies. However, the efficiency of biallelic genetic engineering in transcriptionally inactive genes is still low, unlike that in transcriptionally active genes. To enhance the biallelic homologous recombination efficiency in human ES/iPS cells, we performed screenings of accessorial genes and compounds...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334644/low-level-inorganic-arsenic-exposure-and-neuropsychological-functioning-in-american-indian-elders
#16
Clint R Carroll, Carolyn Noonan, Eva M Garroutte, Ana Navas-Acien, Steven P Verney, Dedra Buchwald
BACKGROUND: Inorganic arsenic at high and prolonged doses is highly neurotoxic. Few studies have evaluated whether long-term, low-level arsenic exposure is associated with neuropsychological functioning in adults. OBJECTIVES: To investigate the association between long-term, low-level inorganic arsenic exposure and neuropsychological functioning among American Indians aged 64-95. METHODS: We assessed 928 participants in the Strong Heart Study by using data on arsenic species in urine samples collected at baseline (1989-1991) and results of standardized tests of global cognition, executive functioning, verbal learning and memory, fine motor functioning, and speed of mental processing administered during comprehensive follow-up evaluations in 2009-2013...
March 18, 2017: Environmental Research
https://www.readbyqxmd.com/read/28334345/effects-of-age-and-gender-on-recall-and-recognition-discriminability
#17
Lisa V Graves, Charles C Moreno, Michelle Seewald, Heather M Holden, Emily J Van Etten, Vedang Uttarwar, Carrie R McDonald, Lisa Delano-Wood, Mark W Bondi, Steven Paul Woods, Dean C Delis, Paul E Gilbert
Objective: Recall and recognition memory abilities are known to decline with increasing age, yet much of the evidence stems from studies that used simple measures of total target recall or recognition. The California Verbal Learning Test-Second Edition (CVLT-II) includes a new measure of recall discriminability that is analogous to recognition discriminability. These discriminability measures yield more thorough assessments of recall and recognition by accounting for intrusion and false positive errors, respectively...
March 17, 2017: Archives of Clinical Neuropsychology: the Official Journal of the National Academy of Neuropsychologists
https://www.readbyqxmd.com/read/28334241/rmats-dvr-rmats-discovery-of-differential-variants-in-rna
#18
Jinkai Wang, Yang Pan, Shihao Shen, Lan Lin, Yi Xing
Motivation: RNA sequences of a gene can have single nucleotide variants (SNVs) due to single nucleotide polymorphisms (SNPs) in the genome, or RNA editing events within the RNA. By comparing RNA-seq data of a given cell type before and after a specific perturbation, we can detect and quantify SNVs in the RNA and discover SNVs with altered frequencies between distinct cellular states. Such differential variants in RNA (DVRs) may reflect allele-specific changes in gene expression or RNA processing, as well as changes in RNA editing in response to cellular perturbations or stimuli...
March 11, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28334154/ethical-issues-of-crispr-technology-and-gene-editing-through-the-lens-of-solidarity
#19
John J Mulvihill, Benjamin Capps, Yann Joly, Tamra Lysaght, Hub A E Zwart, Ruth Chadwick
Background: The avalanche of commentaries on CRISPR-Cas9 technology, a bacterial immune system modified to recognize any short DNA sequence, cut it out, and insert a new one, has rekindled hopes for gene therapy and other applications and raised criticisms of engineering genes in future generations. Sources of data: This discussion draws on articles that emphasize ethics, identified partly through PubMed and Google, 2014-2016. Areas of agreement: CRISPR-Cas9 has taken the pace and prospects for genetic discovery and applications to a high level, stoking anticipation for somatic gene engineering to help patients...
February 23, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/28333536/mom-net-evaluation-of-an-internet-facilitated-cognitive-behavioral-intervention-for-low-income-depressed-mothers
#20
Lisa B Sheeber, Edward G Feil, John R Seeley, Craig Leve, Jeff M Gau, Betsy Davis, Erik Sorensen, Steve Allan
OBJECTIVE: Evaluate an Internet-facilitated cognitive-behavioral treatment intervention for depression, tailored to economically disadvantaged mothers of young children. METHOD: Economically disadvantaged mothers (N = 266) of preschool aged children, who reported elevated levels of depressive symptoms, were randomized to either the 8-session, Internet-facilitated intervention (Mom-Net) or to Motivational Interviewing and Referral to Services (MIRS). Outcomes were measured using the Patient Health Questionnaire 9 (PHQ-9; Spitzer et al...
April 2017: Journal of Consulting and Clinical Psychology
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