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https://www.readbyqxmd.com/read/28202203/female-specific-effect-of-the-bdnf-gene-on-alzheimer-s-disease
#1
Guo-Dong Li, Rui Bi, Deng-Feng Zhang, Min Xu, Rongcan Luo, Dong Wang, Yiru Fang, Tao Li, Chen Zhang, Yong-Gang Yao
Alzheimer's disease (AD) is the most common neurodegenerative disease influenced by genetic and environmental factors. Brain-derived neurotrophic factor (BDNF) plays an important role in the progression of AD, but the genetic association between BDNF and AD remains controversial. In this study, we aimed to explore the potential association between genetic variants in BDNF and AD in Han Chinese and to investigate whether the association is affected by gender. A 3-stage study was conducted to evaluate the genetic association between BDNF and AD...
January 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28196962/spatial-and-temporal-analysis-of-alphavirus-replication-and-assembly-in-mammalian-and-mosquito-cells
#2
Joyce Jose, Aaron B Taylor, Richard J Kuhn
Sindbis virus (SINV [genus Alphavirus, family Togaviridae]) is an enveloped, mosquito-borne virus. Alphaviruses cause cytolytic infections in mammalian cells while establishing noncytopathic, persistent infections in mosquito cells. Mosquito vector adaptation of alphaviruses is a major factor in the transmission of epidemic strains of alphaviruses. Though extensive studies have been performed on infected mammalian cells, the morphological and structural elements of alphavirus replication and assembly remain poorly understood in mosquito cells...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28195208/a-pupal-transcriptomic-screen-identifies-ral-as-a-target-of-store-operated-calcium-entry-in-drosophila-neurons
#3
Shlesha Richhariya, Siddharth Jayakumar, Katharine Abruzzi, Michael Rosbash, Gaiti Hasan
Transcriptional regulation by Store-operated Calcium Entry (SOCE) is well studied in non-excitable cells. However, the role of SOCE has been poorly documented in neuronal cells with more complicated calcium dynamics. Previous reports demonstrated a requirement for SOCE in neurons that regulate Drosophila flight bouts. We refine this requirement temporally to the early pupal stage and use RNA-sequencing to identify SOCE mediated gene expression changes in the developing Drosophila pupal nervous system. Down regulation of dStim, the endoplasmic reticular calcium sensor and a principal component of SOCE in the nervous system, altered the expression of 131 genes including Ral, a small GTPase...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194453/a-paper-based-platform-for-detection-of-viral-rna
#4
Daohong Zhang, David Broyles, Eric A Hunt, Emre Dikici, Sylvia Daunert, Sapna K Deo
Viral detection presents a host of challenges for even the most sensitive analytical techniques, and the complexity of common detection platforms typically preclude portability. With these considerations in mind, we designed a paper microzone plate-based virus detection system for the detection of viral genetic material that can be performed with simple instruments. The sensing system can detect viral cDNA reverse-transcribed from total RNA extraction by utilizing a biotinylated capture probe and an Alexa Fluor® 647-labeled reporter probe...
February 14, 2017: Analyst
https://www.readbyqxmd.com/read/28193205/comparison-of-immunohistochemistry-with-pcr-for-assessment-of-er-pr-and-ki-67-and-prediction-of-pathological-complete-response-in-breast-cancer
#5
Hans-Peter Sinn, Andreas Schneeweiss, Marius Keller, Kornelia Schlombs, Mark Laible, Julia Seitz, Sotirios Lakis, Elke Veltrup, Peter Altevogt, Sebastian Eidt, Ralph M Wirtz, Frederik Marmé
BACKGROUND: Proliferation may predict response to neoadjuvant therapy of breast cancer and is commonly assessed by manual scoring of slides stained by immunohistochemistry (IHC) for Ki-67 similar to ER and PgR. This method carries significant intra- and inter-observer variability. Automatic scoring of Ki-67 with digital image analysis (qIHC) or assessment of MKI67 gene expression with RT-qPCR may improve diagnostic accuracy. METHODS: Ki-67 IHC visual assessment was compared to the IHC nuclear tool (AperioTM) on core biopsies from a randomized neoadjuvant clinical trial...
February 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28192920/diagnosis-therapy-integrative-systems-based-on-magnetic-rna-nanoflowers-for-co-drug-delivery-and-targeted-therapy
#6
Yingshu Guo, Shuang Li, Yujie Wang, Shusheng Zhang
This study was to develop a codrug delivery system for targeting cancer therapy based on magnetic RNA nanoflowers (RNA NF). Compared with traditional nucleic acid structure, convenient separation can be achieved by introducing magnetic nanoparticle (MNP) into RNA NF. Folic acid (FA) modified MNP/RNA NF (FA/MNP/RNA NF) was used as a targeting nanocarrier with excellent biocompatibility to overcome the nonselectivity of MNP/RNA NF. And then, anticancer drug doxorubicin (DOX) and photosensitizer 5, 10, 15, 20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4) binding with RNA NF were used as codrug cargo models...
February 8, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28188885/trpm5-expression-in-the-olfactory-epithelium
#7
Martina Pyrski, Eugenia Eckstein, Andreas Schmid, Bernd Bufe, Jan Weiss, Vladimir Chubanov, Ulrich Boehm, Frank Zufall
The Ca(2+)-activated monovalent cation channel Trpm5 is a key element in chemotransduction of taste receptor cells of the tongue, but the extent to which Trpm5 channels are expressed in olfactory sensory neurons (OSNs) of the main olfactory epithelium (MOE) of adult mice as part of a specific pheromonal detection system is debated. Here, we used a novel Trpm5-IRES-Cre knockin strain to drive Cre recombinase expression, employed previously validated Trpm5 antibodies, performed in situ hybridization experiments to localize Trpm5 RNA, and searched extensively for Trpm5 splice variants in genetically-labeled, Trpm5-expressing MOE cells...
February 7, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28184393/programmable-dna-triple-helix-molecular-switch-in-biosensing-applications-from-in-homogenous-solutions-to-in-living-cells
#8
Pinting Tang, Jing Zheng, Jianru Tang, Dandan Ma, Weijian Xu, Jishan Li, Zhong Cao, Ronghua Yang
Herein, we demonstrated a new gold nanoparticles (AuNPs)-integrated programmable triple-helix molecular switch (THMS) to realize the biosensing of multiple targets from in homogenous solution to in living cells. The results demonstrated that this proposed programmable THMS could be successfully used for imaging multiple messenger RNA (mRNA) in living cells and it significantly extends the scope of the THMS sensing platform.
February 10, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28183814/comparative-proteomics-of-purified-pathogen-vacuoles-correlates-intracellular-replication-of-legionella-pneumophila-with-the-small-gtpase-rap1
#9
Johanna Schm Oumllders, Christian Manske, Andreas Otto, Christine Hoffmann, Bernhard Steiner, Amanda Welin, D Oumlrte Becher, Hubert Hilbi
Legionella pneumophila is an opportunistic bacterial pathogen that causes a severe lung infection termed Legionnaires disease. The pathogen replicates in environmental protozoa as well as in macrophages within a unique membrane-bound compartment, the Legionella-containing-vacuole (LCV). LCV formation requires the bacterial Icm/Dot type IV secretion system, which translocates ca. 300 effector proteins into host cells, where they target distinct host factors. The L. pneumophila pentuple mutant (Δpentuple) lacks 5 gene clusters (31% of the effector proteins) and replicates in macrophages but not in Dictyostelium discoideum amoeba...
February 9, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28179529/differential-disruption-of-nucleocytoplasmic-trafficking-pathways-by-rhinovirus-2a-proteases
#10
Kelly Watters, Bahar Inankur, Jaye C Gardiner, Jay Warrick, Nathan M Sherer, John Yin, Ann C Palmenberg
The RNA rhinoviruses (RV) encode 2A proteases (2A(pro)) that contribute essential polyprotein processing and host-cell shutoff functions during infection, including the cleavage of Phe/Gly-containing nucleoporin proteins (Nups) within nuclear pore complexes (NPC). Within the 3 RV species, multiple divergent genotypes encode diverse 2A(pro) sequences which act differentially on specific Nups. Since only subsets of Phe/Gly motifs, particularly those within Nup62, Nup98 and Nup153, are recognized by transport receptors (karyopherins) when trafficking large molecular cargos through the NPC, the processing preferences of individual 2A(pro) predict RV genotype-specific targeting of NPC pathways and cargos...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28177627/molecular-dynamics-simulations-of-l-rna-involving-homo-and-heterochiral-complexes
#11
Marta Dudek, Joanna Trylska
L-RNA is a mirror image of the naturally occurring D-RNA. We present the first simulations of L-RNA/D-RNA complexes in the AMBER ff10 force field that we modified to account for L-ribonucleotides. To validate the modifications we performed molecular dynamics simulations of several homo- and heterochiral RNA complexes. We did not observe any canonical base pairing in the L-/D- systems but we found many repeatable geometric patterns that suggest possible structural motifs between the heterochiral RNA strands...
February 8, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28177524/in-vivo-expression-of-nurr1-nr4a2a-in-developing-retinal-amacrine-subtypes-in-zebrafish-tg-nr4a2a-egfp-transgenics
#12
Liana Goodings, Jie He, Alasdair Wood, William A Harris, Peter D Currie, Patricia R Jusuf
The Nuclear receptor subfamily 4 group A member 2 (Nr4a2) is crucial for the formation or maintenance of dopaminergic neurons in the central nervous system including the retina, where dopaminergic amacrine cells contribute to visual function. Little is known about which cells express Nr4a2 at which developmental stage. Furthermore, whether Nr4a2 functions in combination with other genes is poorly understood. Thus, we generated a novel transgenic to visualise Nr4a2 expression in vivo during zebrafish retinogenesis...
February 8, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28177223/facial-layer-by-layer-engineering-of-upconversion-nanoparticles-for-gene-delivery-nir-initiated-fret-tracking-and-overcoming-drug-resistance-in-ovarian-cancer
#13
Min Lin, Yan Gao, Thomas J Diefenbach, Jacson K Shen, Francis J Hornicek, Yong Il Park, Feng Xu, Tian Jian Lu, Mansoor M Amiji, Zhenfeng Duan
Development of multidrug resistance (MDR) contributes to the majority of treatment failures in clinical chemotherapy. We report facial layer-by-layer engineered upconversion nanoparticles (UCNPs) for near infrared (NIR) initiated tracking and delivery of small interfering RNA (siRNA) to enhance chemotherapy efficacy by silencing the MDR1 gene and re-sensitizing resistant ovarian cancer cells to drug. Layer-by-layer engineered UCNPs were loaded with MDR1 gene-silencing siRNA (MDR1-siRNA) by electrostatic interaction...
February 8, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28174721/znt2-mediated-zinc-import-into-paneth-cell-granules-is-necessary-for-coordinated-secretion-and-paneth-cell-function%C3%A2-in%C3%A2-mice
#14
Abigail B Podany, Justin Wright, Regina Lamendella, David I Soybel, Shannon L Kelleher
BACKGROUND & AIMS: Defects in Paneth cell (PC) function are associated with microbial dysbiosis and intestinal inflammation. PC granules contain antimicrobial peptides, cytokines, and substantial stores of zinc (Zn). We hypothesized that Zn, transported into the granule through the Zn transporter (ZnT)2, is critical for signature PC functions. METHODS: ZnT2 was localized to PC granules using immunofluorescence and sucrose gradient fractionation in wild-type (wt) mice, and consequences of ZnT2 loss were characterized in ZnT2 knockout (ZnT2ko) mice...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28167528/heat-shock-induced-phosphorylation-of-tar-dna-binding-protein-43-tdp-43-by-mapk-erk-kinase-regulates-tdp-43-function
#15
Wen Li, Ashley N Reeb, Binyan Lin, Praveen Subramanian, Erin E Fey, Catherine R Knoverek, Rachel L French, Eileen H Bigio, Yuna M Ayala
TAR DNA binding protein (TDP-43) is a highly conserved and essential DNA- and RNA-binding protein that controls gene expression through RNA processing, in particular, regulation of splicing. Intracellular aggregation of TDP-43 is a hallmark of amyotrophic lateral sclerosis and ubiquitin-positive frontotemporal lobar degeneration. This TDP-43 pathology is also present in other types of neurodegeneration including Alzheimer's disease. We report here that TDP-43 is a substrate of MEK, a central kinase in the MAPK/ERK signaling pathway...
February 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28161540/genome-organization-in-the-nucleus-from-dynamic-measurements-to-a-functional-model
#16
REVIEW
Anat Vivante, Eugene Brozgol, Irena Bronshtein, Yuval Garini
A biological system is by definition a dynamic environment encompassing kinetic processes that occur at different length scales and time ranges. To explore this type of system, spatial information needs to be acquired at different time scales. This means overcoming significant hurdles, including the need for stable and precise labeling of the required probes and the use of state of the art optical methods. However, to interpret the acquired data, biophysical models that can account for these biological mechanisms need to be developed...
February 1, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28154159/the-t-cell-ift20-interactome-reveals-new-players-in-immune-synapse-assembly
#17
Donatella Galgano, Anna Onnis, Elisa Pappalardo, Federico Galvagni, Oreste Acuto, Cosima T Baldari
Sustained signalling at the immune synapse (IS) requires the synaptic delivery of recycling endosome-associated TCRs. IFT20, a component of the intraflagellar transport system, controls TCR recycling to the IS as a complex with IFT57 and IFT88. Here, we used quantitative mass spectrometry to identify additional interaction partners of IFT20 in Jurkat T cells. In addition to IFT57 and IFT88, the analysis revealed new binding partners, including IFT54, GMAP-210, Arp2/3 complex subunit-3 (ARPC3), COP9 signalosome subunit-1 (CSN1), and ERGIC-53...
February 2, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28152580/quantifying-three-dimensional-morphology-and-rna-from-individual-embryos
#18
Rebecca M Green, Courtney L Leach, Natasha Hoehn, Ralph S Marcucio, Benedikt Hallgrímsson
Quantitative analysis of morphogenesis aids our understanding of developmental processes by providing a method to link changes in shape with cellular and molecular processes. Over the last decade many methods have been developed for 3D imaging of embryos using microCT scanning to quantify the shape of embryos during development. These methods generally involve a powerful, cross-linking fixative such as paraformaldehyde to limit shrinkage during the CT scan. However, the extended time frames that these embryos are incubated in such fixatives prevent use of the tissues for molecular analysis after microCT scanning...
February 2, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28140746/cas9-cpf1-and-c2c1-2-3-what-s-next
#19
Shota Nakade, Takashi Yamamoto, Tetsushi Sakuma
Since the rapid emergence of clustered regulatory interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system, developed as a genome engineering tool in 2012-2013, most researchers in the life science field have had a fixated interest in this fascinating technology. CRISPR-Cas9 is an RNA-guided DNA endonuclease system, which consists of Cas9 nuclease defining a few targeting base via protospacer adjacent motif complexed with easily customizable single guide RNA targeting around 20-bp genomic sequence...
January 31, 2017: Bioengineered
https://www.readbyqxmd.com/read/28139910/cell-selective-bioorthogonal-metabolic-labeling-of-rna
#20
Kim Nguyen, Michael Fazio, Miles Kubota, Sarah Nainar, Chao Feng, Xiang Li, Scott X Atwood, Timothy W Bredy, Robert C Spitale
Stringent chemical methods to profile RNA expression within discrete cellular populations remains a key challenge in biology. To address this issue, we developed a chemical-genetic strategy for metabolic labeling of RNA. Cell-specific labeling of RNA can be profiled and imaged using bioorthogonal chemistry. We anticipate that this platform will provide the community with a much-needed chemical toolset for cell-type specific profiling of cell-specific transcriptomes derived from complex biological systems.
February 7, 2017: Journal of the American Chemical Society
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