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Y Jiang, H Y Chao, X W Zhang, M Zhou, X Z Lu, R Zhang, C He, Q Wang
Objective: To explore the effects and possible mechanisms of the novel pan-FGFR inhibitor BGJ398 on KG-1 cells in vitro. Methods: Effects of BGJ398 on cells proliferation were detected by CCK-8, the apoptosis was assessed by Annexin V-FITC. Reverse transcriptionquantitative polymerase chain reaction (q-PCR) analysis was used to detect the expression of apoptosis-related genes B cell lymphoma-2 (Bcl-2) and caspase-3. Western blotting analysis was performed to explore the proteins expression levels of Bcl-2, caspase-3 and the expression of p-AKT, p-S6K, p-ERK and FGFR1...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
H T Gu, J Y Zhou, T Wu, J Y Zhou
Objective: To investigate the clinical features and prognosis of patients with pulmonary sarcomatoid carcinoma (PSC). Methods: The study retrospectively reviewed the clinical, radiological, pathological characteristics and prognosis of 76 patients with PSC who were treated in the First Affiliated Hospital of Medical School of Zhejiang University from January 2011 to December 2016. Gender, age, smoking history, tumor location, tumor size, lymph node metastasis, distant metastasis, TNM staging and treatment methods were analyzed to determine the factors affecting the prognosis of PSC patients...
March 13, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Héctor Cervera, Silvia Ambrós, Guillermo P Bernet, Guillermo Rodrigo, Santiago F Elena
Determining the fitness of viral genotypes has become a standard practice in virology as it is essential to evaluate their evolutionary potential. Darwinian fitness, defined as the advantage of a given genotype with respect to a reference, is a complex property that captures, in a single figure, differences in performance at every stage of viral infection. To what extent does viral fitness result from specific molecular interactions with host factors and regulatory networks during infection? Can we identify host genes in functional classes whose expression depends on viral fitness? Here, we compared the transcriptomes of tobacco plants infected with seven genotypes of tobacco etch potyvirus (TEV) that differ in fitness...
March 19, 2018: Molecular Biology and Evolution
Ramy K A Sayed, Marisol Fernández-Ortiz, María E Diaz-Casado, Iryna Rusanova, Ibtissem Rahim, Germaine Escames, Luis C López, Doaa M Mokhtar, Darío Acuña-Castroviejo
To gain insight into the mechanism of sarcopenia and the protective effect of melatonin, the gastrocnemius muscles of young (3-4 months), early-aged (12 months), and old-aged (24 months) wild type C57BL/6J female mice, were examined by magnetic resonance and microscopy. Locomotor activity, lactate production and nuclear apoptosis were also assessed. The results support the early onset of sarcopenia at 12 months of age, with reduction of muscle fibers' number, muscle weight/body weight ratio, lactate, and locomotor activity...
March 19, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Helga Ochagavía, Paula Prieto, Roxana Savin, Simon Griffiths, Gustavo A Slafer
Wheat adaptation is affected by Ppd genes, but the role of these alleles on the rates of leaf and spikelet initiation has not been properly analysed. Twelve near isogenic lines (NILs) combining Ppd-1a alleles from different donors introgressed in A, B and/or D genomes were tested under field conditions during two growing seasons together with the wild type, Paragon. Leaf initiation rate was unaffected by Ppd-1a alleles so final leaf number (FLN) was reduced in parallel with reductions in the duration of vegetative phase...
March 17, 2018: Journal of Experimental Botany
Kathy Steppe, Maurits W Vandegehuchte, Bart A E Van de Wal, Pieter Hoste, Adrien Guyot, Catherine E Lovelock, David A Lockington
Mangrove forests depend on a dense structure of sufficiently large trees to fulfil their essential functions as providers of food and wood for animals and people, CO2 sinks and protection from storms. Growth of these forests is known to be dependent on the salinity of soil water, but the influence of foliar uptake of rainwater as a freshwater source, additional to soil water, has hardly been investigated. Under field conditions in Australia, stem diameter variation, sap flow and stem water potential of the grey mangrove (Avicennia marina (Forssk...
March 17, 2018: Tree Physiology
Ji She, Jiangtao Guo, Qingfeng Chen, Weizhong Zeng, Youxing Jiang, Xiao-Chen Bai
The organellar two-pore channel (TPC) functions as a homodimer, in which each subunit contains two homologous Shaker-like six-transmembrane (6-TM)-domain repeats. TPCs belong to the voltage-gated ion channel superfamily and are ubiquitously expressed in animals and plants. Mammalian TPC1 and TPC2 are localized at the endolysosomal membrane, and have critical roles in regulating the physiological functions of these acidic organelles. Here we present electron cryo-microscopy structures of mouse TPC1 (MmTPC1)-a voltage-dependent, phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2 )-activated Na+ -selective channel-in both the apo closed state and ligand-bound open state...
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
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
Gerd Meyer Zu Horste, Dariusz Przybylski, Markus A Schramm, Chao Wang, Alexandra Schnell, Youjin Lee, Raymond Sobel, Aviv Regev, Vijay K Kuchroo
The death receptor Fas removes activated lymphocytes through apoptosis. Previous transcriptional profiling predicted that Fas positively regulates interleukin-17 (IL-17)-producing T helper 17 (Th17) cells. Here, we demonstrate that Fas promoted the generation and stability of Th17 cells and prevented their differentiation into Th1 cells. Mice with T-cell- and Th17-cell-specific deletion of Fas were protected from induced autoimmunity, and Th17 cell differentiation and stability were impaired. Fas-deficient Th17 cells instead developed a Th1-cell-like transcriptional profile, which a new algorithm predicted to depend on STAT1...
March 20, 2018: Immunity
Daehun Park, Unghwi Lee, Eunji Cho, Haiyan Zhao, Jung Ah Kim, Byoung Ju Lee, Philip Regan, Won-Kyung Ho, Kwangwook Cho, Sunghoe Chang
Despite being a highly enriched synaptic vesicle (SV) protein and a candidate gene for autism, the physiological function of SCAMP5 remains mostly enigmatic. Here, using optical imaging and electrophysiological experiments, we demonstrate that SCAMP5 plays a critical role in release site clearance at the active zone. Truncation analysis revealed that the 2/3 loop domain of SCAMP5 directly interacts with adaptor protein 2, and this interaction is critical for its role in release site clearance. Knockdown (KD) of SCAMP5 exhibited pronounced synaptic depression accompanied by a slower recovery of the SV pool...
March 20, 2018: Cell Reports
Seiichiro Amemiya, A David Redish
During decision making, hippocampal activity encodes information sometimes about present and sometimes about potential future plans. The mechanisms underlying this transition remain unknown. Building on the evidence that gamma oscillations at different frequencies (low gamma [LG], 30-55 Hz; high gamma [HG], 60-90 Hz; and epsilon, 100-140 Hz) reflect inputs from different circuits, we identified how changes in those frequencies reflect different information-processing states. Using a unique noradrenergic manipulation by clonidine, which shifted both neural representations and gamma states, we found that future representations depended on gamma components...
March 20, 2018: Cell Reports
Brant Gracia, Hashim M Al-Hashimi, Namita Bisaria, Rhiju Das, Daniel Herschlag, Rick Russell
Large-scale, cooperative rearrangements underlie the functions of RNA in RNA-protein machines and gene regulation. To understand how such rearrangements are orchestrated, we used high-throughput chemical footprinting to dissect a seemingly concerted rearrangement in P5abc RNA, a paradigm of RNA folding studies. With mutations that systematically disrupt or restore putative structural elements, we found that this transition reflects local folding of structural modules, with modest and incremental cooperativity that results in concerted behavior...
March 20, 2018: Cell Reports
Daisuke Shimaoka, Kenneth D Harris, Matteo Carandini
Changes in arousal modulate the activity of mouse sensory cortex, but studies in different mice and different sensory areas disagree on whether this modulation enhances or suppresses activity. We measured this modulation simultaneously in multiple cortical areas by imaging mice expressing voltage-sensitive fluorescent proteins (VSFP). VSFP imaging estimates local membrane potential across large portions of cortex. We used temporal filters to predict local potential from running speed or from pupil dilation, two measures of arousal...
March 20, 2018: Cell Reports
Magdalene I Schlesiger, Brittney L Boublil, Jena B Hales, Jill K Leutgeb, Stefan Leutgeb
The high storage capacity of the episodic memory system relies on distinct representations for events that are separated in time and space. The spatial component of these computations includes the formation of independent maps by hippocampal place cells across environments, referred to as global remapping. Such remapping is thought to emerge by the switching of input patterns from specialized spatially selective cells in medial entorhinal cortex (mEC), such as grid and border cells. Although it has been shown that acute manipulations of mEC firing patterns are sufficient for inducing hippocampal remapping, it remains unknown whether specialized spatial mEC inputs are necessary for the reorganization of hippocampal spatial representations...
March 20, 2018: Cell Reports
Manami Yamashita, Shin-Ya Kawaguchi, Tetsuya Hori, Tomoyuki Takahashi
Synaptic efficacy plays crucial roles in neuronal circuit operation and synaptic plasticity. Presynaptic determinants of synaptic efficacy are neurotransmitter content in synaptic vesicles and the number of vesicles undergoing exocytosis at a time. Bursts of presynaptic firings depress synaptic efficacy, mainly due to depletion of releasable vesicles, whereas recovery from strong depression is initiated by endocytic vesicle retrieval followed by refilling of vesicles with neurotransmitter. We washed out presynaptic cytosolic GABA to induce a rundown of IPSCs at cerebellar inhibitory cell pairs in slices from rats and then allowed fast recovery by elevating GABA concentration using photo-uncaging...
March 20, 2018: Cell Reports
Xu Zheng, Ali Beyzavi, Joanna Krakowiak, Nikit Patel, Ahmad S Khalil, David Pincus
Clonal populations of cells exhibit cell-to-cell variation in the transcription of individual genes. In addition to this noise in gene expression, heterogeneity in the proteome and the proteostasis network expands the phenotypic diversity of a population. Heat shock factor 1 (Hsf1) regulates chaperone gene expression, thereby coupling transcriptional noise to proteostasis. Here we show that cell-to-cell variation in Hsf1 activity is an important determinant of phenotypic plasticity. Budding yeast cells with high Hsf1 activity were enriched for the ability to acquire resistance to an antifungal drug, and this enrichment depended on Hsp90, a known phenotypic capacitor and canonical Hsf1 target...
March 20, 2018: Cell Reports
Marie-Charlotte Gandolphe, Bérénice Lecluyse, Claire Triquet, Emmanuel Brunelle, Jean-Paul Duparcq, Jean-Louis Nandrino
OBJECTIVES: Impairments in social cognition have been described as playing a major role in the maintenance of addictive behavior in substance abusers. This study aimed to investigate the Theory of Mind (ToM) ability of opiate-dependent (OD) patients and to explore whether TOM ability was correlated with length of substance abuse, age at onset of substance abuse and length of abstinence. METHODS: OD patients (N = 29) and non-dependent individuals (NDI) (N = 29) were submitted to the Theory of Mind Assessment Scale (Th...
March 12, 2018: Comprehensive Psychiatry
Hang Ren, Cameron G Cheyne, Aaron M Fleming, Cynthia J Burrows, Henry S White
Measurement of single-molecule reactions can elucidate microscopic mechanisms that are often hidden from ensemble analysis. Herein, we report the acid-base titration of a single DNA duplex confined within the wild-type α-hemolysin (α-HL) nanopore for up to 3 h, while monitoring the ionic current through the nanopore. Modulation between two states in the current-time trace for duplexes containing the C:C mismatch in proximity to the latch constriction of α-HL is attributed to the base flipping of the C:C mismatch...
March 21, 2018: Journal of the American Chemical Society
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