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J J Zhao, Y L Zhang, S J Zhang, J Zhou, F K Yu, Y L Zu, H F Zhao, Z Li, Y P Song
Objective: To investigate the molecular-cytogenetic characterization and impact on tyrosine kinase inhibitors (TKIs) therapy in chronic phase of chronic myeloid leukemia (CML-CP) patients with variant Ph chromosome (vPh). Methods: The clinical data of 32 patients with vPh chromosomes were collected and compared with 703 patients with typical Ph chromosome in newly diagnosed CML-CP who were on first-line imatinib (IM) and with BCR-ABL transcript of P210. Results: There was no significant difference in demographic and hematological characteristics between vPh and classic Ph patients...
March 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
J Feng, X Y Gong, Y J Jia, K Q Liu, Y Li, X B Dong, Q Y Fang, K Ru, Q H Li, H J Wang, X L Zhao, Y N Jia, Y Song, Z Tian, M Wang, K J Tang, J X Wang, Y C Mi
Objective: To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis. Methods: DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Mitsuko Kishi-Kaboshi, Shigemi Seo, Akira Takahashi, Hirohiko Hirochika
Phenylpropanoids including diverse compounds, such as monolignols and hydroxycinnamic acids (HCAAs), are essential for land plants to protect them against abiotic stresses, and create physical and chemical barriers to pathogen infection. However, the production control of these compounds against to pathogens has been poorly understood. Previously we showed that a MAMP (microbe-associated molecular pattern) -responsive MAPK (mitogen-activated protein kinase) cascade (MKK4-MPK3/MPK6) comprehensively induced the expression of cinnamate/monolignol synthesis genes in rice cells...
March 19, 2018: Plant & Cell Physiology
William H Curley, Peter B Forgacs, Henning U Voss, Mary M Conte, Nicholas D Schiff
Patients with severe brain injury are difficult to assess and frequently subject to misdiagnosis. 'Cognitive motor dissociation' is a term used to describe a subset of such patients with preserved cognition as detected with neuroimaging methods but not evident in behavioural assessments. Unlike the locked-in state, cognitive motor dissociation after severe brain injury is prominently marked by concomitant injuries across the cerebrum in addition to limited or no motoric function. In the present study, we sought to characterize the EEG signals used as indicators of cognition in patients with disorders of consciousness and examine their reliability for potential future use to re-establish communication...
March 19, 2018: Brain: a Journal of Neurology
Ulrike Bechtold, John N Ferguson, Philip M Mullineaux
The emergence of Arabidopsis as a model species and the availability of genetic and genomic resources have resulted in the identification and detailed characterisation of abiotic stress signalling pathways. However, this has led only to limited success in engineering abiotic stress tolerance in crops. This is because there needs to be a deeper understanding in how to combine resistances to a range of stresses with growth and productivity. The natural variation and genomic resources of Arabidopsis thaliana (Arabidopsis) is a great asset to understand the mechanisms of multiple stress tolerances...
March 17, 2018: Journal of Experimental Botany
Wei Zhang, Guihai Feng, Libin Wang, Fei Teng, Liu Wang, Wei Li, Ying Zhang, Qi Zhou
The generation of induced pluripotent stem cells (iPSCs) offers a great opportunity in research and regenerative medicine. The current poor efficiency and incomplete mechanistic understanding of the reprogramming process hampers the clinical application of iPSCs. MeCP2 connects histone modification and DNA methylation, which are key changes of somatic cell reprogramming. However, the role of MeCP2 in cell reprogramming has not been examined. In this study, we found that MeCP2 deficiency enhanced reprogramming efficiency and stimulated cell proliferation through regulating cell cycle protein expression in the early stage of reprogramming...
March 19, 2018: Journal of Molecular Cell Biology
Mi-Young Lee, Sung Hoon Kim, Young Sang Oh, Seung-Ho Heo, Kang-Hyun Kim, Hee Dong Chae, Chung-Hoon Kim, Byung Moon Kang
STUDY QUESTION: Does interleukin-32 (IL-32) play a role in the pathogenesis of endometriosis? SUMMARY ANSWER: IL-32 might be involved in the pathogenesis of endometriosis through increased viability, proliferation and invasion of endometrial cells. WHAT IS KNOWN ALREADY: Endometriosis is characterized as a chronic inflammatory disease and several proinflammatory cytokines are suggested to be involved in its pathogenesis and pathophysiology...
March 19, 2018: Human Reproduction
Suresh Venkateswaran, Jarod Prince, David J Cutler, Urko M Marigorta, David T Okou, Sampath Prahalad, David Mack, Brendan Boyle, Thomas Walters, Anne Griffiths, Cary G Sauer, Neal LeLeiko, David Keljo, James Markowitz, Susan S Baker, Joel Rosh, Marian Pfefferkorn, Melvin B Heyman, Ashish Patel, Anthony Otley, Robert Baldassano, Joshua Noe, Paul Rufo, Maria Oliva-Hemker, Sonia Davis, Michael E Zwick, Greg Gibson, Lee A Denson, Jeffrey Hyams, Subra Kugathasan
Background: The genetic contributions to pediatric onset ulcerative colitis (UC), characterized by severe disease and extensive colonic involvement, are largely unknown. In adult onset UC, Genome Wide Association Study (GWAS) has identified numerous loci, most of which have a modest susceptibility risk (OR 0.84-1.14), with the exception of the human leukocyte antigen (HLA) region on Chromosome 6 (OR 3.59). Method: To study the genetic contribution to exclusive pediatric onset UC, a GWAS was performed on 466 cases with 2099 healthy controls using UK Biobank array...
March 19, 2018: Inflammatory Bowel Diseases
Carlos A Campos, Anna J Bowen, Carolyn W Roman, Richard D Palmiter
Animals must respond to various threats to survive. Neurons that express calcitonin gene-related peptide in the parabrachial nucleus (CGRPPBN neurons) relay sensory signals that contribute to satiation and pain-induced fear behaviour, but it is unclear how they encode these distinct processes. Here, by recording calcium transients in vivo from individual neurons in mice, we show that most CGRPPBN neurons are activated by noxious cutaneous (shock, heat, itch) and visceral stimuli (lipopolysaccharide). The same neurons are inhibited during feeding, but become activated during satiation, consistent with evidence that CGRPPBN neurons prevent overeating...
March 21, 2018: Nature
Misty R Riddle, Ariel C Aspiras, Karin Gaudenz, Robert Peuß, Jenny Y Sung, Brian Martineau, Megan Peavey, Andrew C Box, Julius A Tabin, Suzanne McGaugh, Richard Borowsky, Clifford J Tabin, Nicolas Rohner
Periodic food shortages are a major challenge faced by organisms in natural habitats. Cave-dwelling animals must withstand long periods of nutrient deprivation, as-in the absence of photosynthesis-caves depend on external energy sources such as seasonal floods. Here we show that cave-adapted populations of the Mexican tetra, Astyanax mexicanus, have dysregulated blood glucose homeostasis and are insulin-resistant compared to river-adapted populations. We found that multiple cave populations carry a mutation in the insulin receptor that leads to decreased insulin binding in vitro and contributes to hyperglycaemia...
March 21, 2018: Nature
Veronica Mendoza-Reinoso, Annemiek Beverdam
The skin constantly self-renews throughout adult life. Wnt/β-catenin signaling plays a key role in promoting keratinocyte proliferation in the hair follicles and in the interfollicular epidermis. A recent report demonstrated that epidermal YAP activity drives β-catenin activation to promote keratinocyte proliferation in the murine skin. However, it remains unclear whether this is caused by paracrine activation of canonical Wnt signaling or through other YAP/β-catenin regulatory interactions. In the present study, we found that XAV939-inhibition of canonical WNT signaling in skin of YAP2-5SA-ΔC mice resulted in diminished β-catenin activation, reduced keratinocyte proliferation, and a mitigation of the hyperplastic abnormalities in the interfollicular epidermis, signifying a canonical WNT ligand-dependent mechanism...
March 10, 2018: Stem Cell Research
Karl Kuntzelman, L Jack Rhodes, Lillian N Harrington, Vladimir Miskovic
There is a broad family of statistical methods for capturing time series regularity, with increasingly widespread adoption by the neuroscientific community. A common feature of these methods is that they permit investigators to quantify the entropy of brain signals - an index of unpredictability/complexity. Despite the proliferation of algorithms for computing entropy from neural time series data there is scant evidence concerning their relative stability and efficiency. Here we evaluated several different algorithmic implementations (sample, fuzzy, dispersion and permutation) of multiscale entropy in terms of their stability across sessions, internal consistency and computational speed, accuracy and precision using a combination of electroencephalogram (EEG) and synthetic 1/ƒ noise signals...
March 18, 2018: Brain and Cognition
Lorraine A O'Reilly, Tracy L Putoczki, Lisa A Mielke, Jun T Low, Ann Lin, Adele Preaudet, Marco J Herold, Kelvin Yaprianto, Lin Tai, Andrew Kueh, Guido Pacini, Richard L Ferrero, Raffi Gugasyan, Yifang Hu, Michael Christie, Stephen Wilcox, Raelene Grumont, Michael D W Griffin, Liam O'Connor, Gordon K Smyth, Mathias Ernst, Paul Waring, Steve Gerondakis, Andreas Strasser
Polymorphisms in NFKB1 that diminish its expression have been linked to human inflammatory diseases and increased risk for epithelial cancers. The underlying mechanisms are unknown, and the link is perplexing given that NF-κB signaling reportedly typically exerts pro-tumorigenic activity. Here we have shown that NF-κB1 deficiency, even loss of a single allele, resulted in spontaneous invasive gastric cancer (GC) in mice that mirrored the histopathological progression of human intestinal-type gastric adenocarcinoma...
March 20, 2018: Immunity
Xin Li, Adeline Gadzinsky, Liying Gong, Haijun Tong, Virginie Calderon, Yue Li, Daisuke Kitamura, Ulf Klein, Wallace Y Langdon, Fajian Hou, Yong-Rui Zou, Hua Gu
Selective expansion of high-affinity antigen-specific B cells in germinal centers (GCs) is a key event in antibody affinity maturation. GC B cells with improved affinity can either continue affinity-driven selection or exit the GC to differentiate into plasma cells (PCs) or memory B cells. Here we found that deleting E3 ubiquitin ligases Cbl and Cbl-b (Cbls) in GC B cells resulted in the early exit of high-affinity antigen-specific B cells from the GC reaction and thus impaired clonal expansion. Cbls were highly expressed in GC light zone (LZ) B cells, where they promoted the ubiquitination and degradation of Irf4, a transcription factor facilitating PC fate choice...
March 20, 2018: Immunity
Antonella Montinaro, Henning Walczak
Constitutively activated NF-κB signaling has long been known to be oncogenic. In this issue of Immunity, O'Reilly et al. (2018) unveil a link between loss of NF-κB1, aberrant STAT1 signaling, sterile inflammation, and the increased expression of immune checkpoint molecules as cancer drivers.
March 20, 2018: Immunity
Elizabeth M Steinert, Navdeep S Chandel
Memory CD8+ T cells mediate protective secondary immune responses. In this issue, Bantug et al. (2018) demonstrate that mTORC2-AKT-GSK3β signaling at mitochondria-ER contact sites enables the TCA cycle flux that is necessary for memory CD8+ T cells to produce IFN-γ.
March 20, 2018: Immunity
Chong Sun, Riccardo Mezzadra, Ton N Schumacher
Expression of programmed death-ligand 1 (PD-L1) is frequently observed in human cancers. Binding of PD-L1 to its receptor PD-1 on activated T cells inhibits anti-tumor immunity by counteracting T cell-activating signals. Antibody-based PD-1-PD-L1 inhibitors can induce durable tumor remissions in patients with diverse advanced cancers, and thus expression of PD-L1 on tumor cells and other cells in the tumor microenviroment is of major clinical relevance. Here we review the roles of the PD-1-PD-L1 axis in cancer, focusing on recent findings on the mechanisms that regulate PD-L1 expression at the transcriptional, posttranscriptional, and protein level...
March 20, 2018: Immunity
Abigail K Corona, Holly M Saulsbery, Angel F Corona Velazquez, William T Jackson
Enterovirus D68 (EV-D68) is a medically important respiratory plus-strand RNA virus of children that has been linked to acute flaccid myelitis. We have determined that EV-D68 induces autophagic signaling and membrane formation. Autophagy, a homeostatic degradative process that breaks down protein aggregates and damaged organelles, promotes replication of multiple plus-strand viruses. Induction of autophagic signals promotes EV-D68 replication, but the virus inhibits the downstream degradative steps of autophagy in multiple ways...
March 20, 2018: Cell Reports
Liansheng Liu, Jinqiu Lu, Xiaoling Li, Ailing Wu, Qingzhe Wu, Mujun Zhao, Nan Tang, Hai Song
Intracellular transport of membranous organelles and protein complexes to various destinations is fundamental to signaling transduction and cellular function. The cytoplasmic dynein motor and its regulatory proteins LIS1 and NDE1 are required for transporting a variety of cellular cargos along the microtubule network. In this study, we show that deletion of Lis1 in developing lung endoderm and limb mesenchymal cells causes agenesis of the lungs and limbs. In both mutants, there is increased cell death and decreased fibroblast growth factor (FGF) signaling activity...
March 20, 2018: Cell Reports
Walderik W Zomerman, Sabine L A Plasschaert, Siobhan Conroy, Frank J Scherpen, Tiny G J Meeuwsen-de Boer, Harm J Lourens, Sergi Guerrero Llobet, Marlinde J Smit, Lorian Slagter-Menkema, Annika Seitz, Corrie E M Gidding, Esther Hulleman, Pieter Wesseling, Lisethe Meijer, Leon C van Kempen, Anke van den Berg, Daniël O Warmerdam, Frank A E Kruyt, Floris Foijer, Marcel A T M van Vugt, Wilfred F A den Dunnen, Eelco W Hoving, Victor Guryev, Eveline S J M de Bont, Sophia W M Bruggeman
The brain cancer medulloblastoma consists of different transcriptional subgroups. To characterize medulloblastoma at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a large cohort of SHH (Sonic Hedgehog), group 3, and group 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence and resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. The second profile showed enrichment for DNA damage, as well as apoptotic and neuronal signaling...
March 20, 2018: Cell Reports
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