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https://www.readbyqxmd.com/read/29346835/two-citrate-transporters-coordinately-regulate-citrate-secretion-from-rice-bean-root-tip-under-aluminum-stress
#1
Mei Ya Liu, He Qiang Lou, Wei Wei Chen, Miguel A Piñeros, Jia Meng Xu, Wei Fan, Leon V Kochian, Shao Jian Zheng, Jian Li Yang
Al-induced organic acid secretion from the root apex is an important Al resistance mechanism. However, it remains unclear how plants fine-tune root organic acid secretion which can contribute significantly to the loss of fixed carbon from the plant. Here, we demonstrate that Al-induced citrate secretion from the rice bean root apex is biphasic, consisting of an early phase with low secretion and a later phase of large citrate secretion. We isolated and characterized VuMATE2 as a possible second citrate transporter in rice bean functioning in tandem with VuMATE1, which we previously identified...
January 18, 2018: Plant, Cell & Environment
https://www.readbyqxmd.com/read/29346833/phase-1b-trial-of-ficlatuzumab-a-humanized-hepatocyte-growth-factor-inhibitory-monoclonal-antibody-in-combination-with-gefitinib-in-asian-patients-with-nsclc
#2
Eng-Huat Tan, Wan-Teck Lim, Myung-Ju Ahn, Quan-Sing Ng, Jin Seok Ahn, Daniel Shao-Weng Tan, Jong-Mu Sun, May Han, Francis C Payumo, Krista McKee, Wei Yin, Marc Credi, Shefali Agarwal, Jaroslaw Jac, Keunchil Park
Hepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV-299; SCH 900105), a humanized IgG1 κ HGF inhibitory monoclonal antibody, prevents HGF/c-Met pathway ligand-mediated activation. This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non-small cell lung cancer (NSCLC)...
January 18, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29346789/mentalization-and-self-efficacy-as-mediators-between-psychological-symptom-severity-and-disabilities-in-activities-and-participation-in-psychotherapy-patients
#3
Thomas Probst, Maria Dehoust, Anna Levke Brütt, Holger Schulz, Christoph Pieh, Sylke Andreas
BACKGROUND: Psychotherapy patients can be more or less disabled by their psychological symptoms. The present study investigated whether mentalization and self-efficacy contribute to the association between psychological symptom severity and disabilities in activities and participation. METHODS: The data of 216 psychotherapy inpatients were examined in a cross-sectional design. Bootstrapping-enhanced mediation analyses were performed to investigate whether self-efficacy and mentalization are mediators between psychological symptom severity and disabilities in activities and participation...
January 19, 2018: Psychopathology
https://www.readbyqxmd.com/read/29346788/vitamin-d-classic-and-novel-actions
#4
Ángel Gil, Julio Plaza-Diaz, María Dolores Mesa
BACKGROUND: Classically, vitamin D has been implicated in bone health by promoting calcium absorption in the gut and maintenance of serum calcium and phosphate concentrations, as well as by its action on bone growth and reorganization through the action of osteoblasts and osteoclasts cells. However, in the last 2 decades, novel actions of vitamin D have been discovered. The present report summarizes both classic and novel actions of vitamin D. SUMMARY: 1,25(OH)2 vitamin D, the active metabolite of vitamin D, also known as calcitriol, regulates not only calcium and phosphate homeostasis but also cell proliferation and differentiation, and has a key a role to play in the responses of the immune and nervous systems...
January 18, 2018: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/29346777/prrt2-regulates-synaptic-fusion-by-directly-modulating-snare-complex-assembly
#5
Jeff Coleman, Ouardane Jouannot, Sathish K Ramakrishnan, Maria N Zanetti, Jing Wang, Vincenzo Salpietro, Henry Houlden, James E Rothman, Shyam S Krishnakumar
Mutations in proline-rich transmembrane protein 2 (PRRT2) are associated with a range of paroxysmal neurological disorders. PRRT2 predominantly localizes to the pre-synaptic terminals and is believed to regulate neurotransmitter release. However, the mechanism of action is unclear. Here, we use reconstituted single vesicle and bulk fusion assays, combined with live cell imaging of single exocytotic events in PC12 cells and biophysical analysis, to delineate the physiological role of PRRT2. We report that PRRT2 selectively blocks the trans SNARE complex assembly and thus negatively regulates synaptic vesicle priming...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346776/loss-of-an-androgen-inactivating-and-isoform-specific-hsd17b4-splice-form-enables-emergence-of-castration-resistant-prostate-cancer
#6
Hyun-Kyung Ko, Michael Berk, Yoon-Mi Chung, Belinda Willard, Rohan Bareja, Mark Rubin, Andrea Sboner, Nima Sharifi
Castration-resistant prostate cancer (CRPC) requires tumors to engage metabolic mechanisms that allow sustained testosterone and/or dihydrotestosterone to stimulate progression. 17β-Hydroxysteroid dehydrogenase type 4 (17βHSD4), encoded by HSD17B4, is thought to inactivate testosterone and dihydrotestosterone by converting them to their respective inert 17-keto steroids. Counterintuitively, HSD17B4 expression increases in CRPC and predicts poor prognosis. Here, we show that, of five alternative splice forms, only isoform 2 encodes an enzyme capable of testosterone and dihydrotestosterone inactivation...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346774/mannose-receptor-1-restricts-hiv-particle-release-from-infected-macrophages
#7
Sayaka Sukegawa, Eri Miyagi, Fadila Bouamr, Helena Farkašová, Klaus Strebel
Human mannose receptor 1 (hMRC1) is expressed on the surface of most tissue macrophages, dendritic cells, and select lymphatic or liver endothelial cells. HMRC1 contributes to the binding of HIV-1 to monocyte-derived macrophages (MDMs) and is involved in the endocytic uptake of HIV-1 into these cells. Here, we identify hMRC1 as an antiviral factor that inhibits virus release through a bone marrow stromal antigen 2 (BST-2)-like mechanism. Virions produced in the presence of hMRC1 accumulated in clusters at the cell surface but were fully infectious...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346771/rapid-turnover-of-cortical-ncam1-regulates-synaptic-reorganization-after-peripheral-nerve-injury
#8
Hyoung-Gon Ko, Jun-Hyeok Choi, Dong Ik Park, SukJae Joshua Kang, Chae-Seok Lim, Su-Eon Sim, Jaehoon Shim, Ji-Il Kim, Siyong Kim, Tae-Hyeok Choi, Sanghyun Ye, Jaehyun Lee, Pojeong Park, Somi Kim, Jeehaeh Do, Jihye Park, Md Ariful Islam, Hyun Jeong Kim, Christoph W Turck, Graham L Collingridge, Min Zhuo, Bong-Kiun Kaang
Peripheral nerve injury can induce pathological conditions that lead to persistent sensitized nociception. Although there is evidence that plastic changes in the cortex contribute to this process, the underlying molecular mechanisms are unclear. Here, we find that activation of the anterior cingulate cortex (ACC) induced by peripheral nerve injury increases the turnover of specific synaptic proteins in a persistent manner. We demonstrate that neural cell adhesion molecule 1 (NCAM1) is one of the molecules involved and show that it mediates spine reorganization and contributes to the behavioral sensitization...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346769/switching-on-depression-and-potentiation-in-the-cerebellum
#9
Andrew R Gallimore, Taegon Kim, Keiko Tanaka-Yamamoto, Erik De Schutter
Long-term depression (LTD) and long-term potentiation (LTP) in the cerebellum are important for motor learning. However, the signaling mechanisms controlling whether LTD or LTP is induced in response to synaptic stimulation remain obscure. Using a unified model of LTD and LTP at the cerebellar parallel fiber-Purkinje cell (PF-PC) synapse, we delineate the coordinated pre- and postsynaptic signaling that determines the direction of plasticity. We show that LTP is the default response to PF stimulation above a well-defined frequency threshold...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346768/activation-of-ampk-regulated-crh-neurons-in-the-pvh-is-sufficient-and-necessary-to-induce-dietary-preference-for-carbohydrate-over-fat
#10
Shiki Okamoto, Tatsuya Sato, Michihiro Tateyama, Haruaki Kageyama, Yuko Maejima, Masanori Nakata, Satoshi Hirako, Takashi Matsuo, Sanda Kyaw, Tetsuya Shiuchi, Chitoku Toda, Udval Sedbazar, Kumiko Saito, Nur Farehan Asgar, Boyang Zhang, Shigefumi Yokota, Kenta Kobayashi, Fabienne Foufelle, Pascal Ferré, Masamitsu Nakazato, Hiroaki Masuzaki, Seiji Shioda, Toshihiko Yada, Barbara B Kahn, Yasuhiko Minokoshi
Food selection is essential for metabolic homeostasis and is influenced by nutritional state, food palatability, and social factors such as stress. However, the mechanism responsible for selection between a high-carbohydrate diet (HCD) and a high-fat diet (HFD) remains unknown. Here, we show that activation of a subset of corticotropin-releasing hormone (CRH)-positive neurons in the rostral region of the paraventricular hypothalamus (PVH) induces selection of an HCD over an HFD in mice during refeeding after fasting, resulting in a rapid recovery from the change in ketone metabolism...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346766/cell-type-specificity-of-callosally-evoked-excitation-and-feedforward-inhibition-in-the-prefrontal-cortex
#11
Paul G Anastasiades, Joseph J Marlin, Adam G Carter
Excitation and inhibition are highly specific in the cortex, with distinct synaptic connections made onto subtypes of projection neurons. The functional consequences of this selective connectivity depend on both synaptic strength and the intrinsic properties of targeted neurons but remain poorly understood. Here, we examine responses to callosal inputs at cortico-cortical (CC) and cortico-thalamic (CT) neurons in layer 5 of mouse prelimbic prefrontal cortex (PFC). We find callosally evoked excitation and feedforward inhibition are much stronger at CT neurons compared to neighboring CC neurons...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346765/characterization-of-endothelial-cells-associated-with-hematopoietic-niche-formation-in-humans-identifies-il-33-as-an-anabolic-factor
#12
Keane Jared Guillaume Kenswil, Adrian Christopher Jaramillo, Zhen Ping, Si Chen, Remco Michiel Hoogenboezem, Maria Athina Mylona, Maria Niken Adisty, Eric Moniqué Johannes Bindels, Pieter Koen Bos, Hans Stoop, King Hong Lam, Bram van Eerden, Tom Cupedo, Marc Hermanus Gerardus Petrus Raaijmakers
Bone marrow formation requires an orchestrated interplay between osteogenesis, angiogenesis, and hematopoiesis that is thought to be mediated by endothelial cells. The nature of the endothelial cells and the molecular mechanisms underlying these events remain unclear in humans. Here, we identify a subset of endoglin-expressing endothelial cells enriched in human bone marrow during fetal ontogeny and upon regeneration after chemotherapeutic injury. Comprehensive transcriptional characterization by massive parallel RNA sequencing of these cells reveals a phenotypic and molecular similarity to murine type H endothelium and activation of angiocrine factors implicated in hematopoiesis, osteogenesis, and angiogenesis...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346759/nf-%C3%AE%C2%BAb-chromatin-interactions-drive-diverse-phenotypes-by-modulating-transcriptional-noise
#13
Victor C Wong, Victor L Bass, M Elise Bullock, Arvind K Chavali, Robin E C Lee, Walther Mothes, Suzanne Gaudet, Kathryn Miller-Jensen
Noisy gene expression generates diverse phenotypes, but little is known about mechanisms that modulate noise. Combining experiments and modeling, we studied how tumor necrosis factor (TNF) initiates noisy expression of latent HIV via the transcription factor nuclear factor κB (NF-κB) and how the HIV genomic integration site modulates noise to generate divergent (low-versus-high) phenotypes of viral activation. We show that TNF-induced transcriptional noise varies more than mean transcript number and that amplification of this noise explains low-versus-high viral activation...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346754/input-specific-nmdar-dependent-potentiation-of-dendritic-gabaergic-inhibition
#14
Chiayu Q Chiu, James S Martenson, Maya Yamazaki, Rie Natsume, Kenji Sakimura, Susumu Tomita, Steven J Tavalin, Michael J Higley
Preservation of a balance between synaptic excitation and inhibition is critical for normal brain function. A number of homeostatic cellular mechanisms have been suggested to play a role in maintaining this balance, including long-term plasticity of GABAergic inhibitory synapses. Many previous studies have demonstrated a coupling of postsynaptic spiking with modification of perisomatic inhibition. Here, we demonstrate that activation of NMDA-type glutamate receptors leads to input-specific long-term potentiation of dendritic inhibition mediated by somatostatin-expressing interneurons...
January 17, 2018: Neuron
https://www.readbyqxmd.com/read/29346752/epitranscriptomic-m6a-regulation-of-axon-regeneration-in-the-adult-mammalian-nervous-system
#15
Yi-Lan Weng, Xu Wang, Ran An, Jessica Cassin, Caroline Vissers, Yuanyuan Liu, Yajing Liu, Tianlei Xu, Xinyuan Wang, Samuel Zheng Hao Wong, Jessica Joseph, Louis C Dore, Qiang Dong, Wei Zheng, Peng Jin, Hao Wu, Bin Shen, Xiaoxi Zhuang, Chuan He, Kai Liu, Hongjun Song, Guo-Li Ming
N6-methyladenosine (m6A) affects multiple aspects of mRNA metabolism and regulates developmental transitions by promoting mRNA decay. Little is known about the role of m6A in the adult mammalian nervous system. Here we report that sciatic nerve lesion elevates levels of m6A-tagged transcripts encoding many regeneration-associated genes and protein translation machinery components in the adult mouse dorsal root ganglion (DRG). Single-base resolution m6A-CLIP mapping further reveals a dynamic m6A landscape in the adult DRG upon injury...
January 17, 2018: Neuron
https://www.readbyqxmd.com/read/29346746/shh-ushing-midline-crossing-through-remote-protein-transport
#16
Eloísa Herrera, Austen A Sitko, Paola Bovolenta
Shh contributes to neural circuit formation with different mechanisms. In this issue, Peng and colleagues (2018) identify a novel trans-axonal mechanism by which Shh derived from contralateral projecting retinal ganglion cells prevents midline crossing of Boc-expressing ipsilateral axons at the optic chiasm.
January 17, 2018: Neuron
https://www.readbyqxmd.com/read/29346735/mechanisms-of-modulation-of-calcium-phosphate-pathological-mineralization-by-mobile-and-immobile-small-molecule-inhibitors
#17
Meng Li, Jing Zhang, Lijun Wang, Baoshan Wang, Christine V Putnis
Potential pathways for inhibiting crystal growth are either via disrupting local microenvironments surrounding crystal-solution interfaces or physically blocking solute molecule attachment. However, the actual mode of inhibition may be more complicated due to the characteristic time scale for the inhibitor adsorption and relaxation to a well-bound state at crystal surfaces. Here we demonstrate the role of citrate (CA) and hydroxycitrate (HCA) in brushite (DCPD, CaHPO4·2H2O) crystallization over a broad range of both inhibitor concentrations and supersaturations by in situ atomic force microscopy (AFM)...
January 18, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29346723/shear-induced-brittle-failure-along-grain-boundaries-in-boron-carbide
#18
Xiaokun Yang, Shawn P Coleman, Jerry Lasalvia, William A Goddard, Qi An
The roles of grain boundaries (GB) in mechanical properties have been examined extensively for metals and alloys; however, for covalent solids their roles in deformation response to applied stress are much less established. We consider here the unusual ceramic, boron carbide (B4C), which is very hard and lightweight but exhibits brittle impact behavior. We used quantum mechanics (QM) simulations to determine the mechanical response in the atomistic structures at GBs under pure shear and also with biaxial shear deformation that mimics indentation stress conditions...
January 18, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29346720/nanoscale-control-of-molecular-self-assembly-induced-by-plasmonic-hot-electron-dynamics
#19
Sabrina Simoncelli, Yi Li, Emiliano Cortes, Stefan A Maier
Self-assembly processes allow designing and creating complex nanostructures using molecules as building blocks and surfaces as scaffolds. This autonomous driven construction is possible due to a complex thermodynamic balance of molecule-surface interactions. As such, nanoscale guidance and control over this process is hard to achieve. Here we use the highly localized light-to-chemical-energy conversion of plasmonic materials to spatially cleave Au-S bonds on pre-determined locations within a single nanoparticle, enabling a high degree of control over this archetypal system for molecular self-assembly...
January 18, 2018: ACS Nano
https://www.readbyqxmd.com/read/29346719/a-tunable-molten-salt-route-for-scalable-synthesis-of-ultrathin-amorphous-carbon-nanosheets-as-high-performance-anode-materials-for-lithium-ion-batteries
#20
Yixian Wang, Wei Tian, Luhai Wang, Haoran Zhang, Jialiang Liu, Tingyue Peng, Lei Pan, Xiaobo Wang, Mingbo Wu
Amorphous carbon is regarded as a promising alternative to commercial graphite as the lithium-ion battery anode due to its capability to reversibly store more lithium ions. However, the structural disorder with a large number of defects can lead to low electrical conductivity of the amorphous carbon, thus limiting its application for high power output. Herein, ultrathin amorphous carbon nanosheets were prepared from petroleum asphalt through tuning the carbonization temperature in a molten-salt medium. The amorphous nanostructure with expanded carbon interlayer spacing can provide substantial active sites for lithium storage while the two-dimensional (2D) morphology can facilitate fast electrical conductivity...
January 18, 2018: ACS Applied Materials & Interfaces
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