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Uptake transporters

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https://www.readbyqxmd.com/read/28550259/transport-of-non-transferrin-bound-iron-to-the-brain-implications-for-alzheimer-s-disease
#1
Ajai K Tripathi, Shilpita Karmakar, Abhishek Asthana, Ajay Ashok, Vilok Desai, Shounak Baksi, Neena Singh
A direct correlation between brain iron and Alzheimer's disease (AD) raises questions regarding the transport of non-transferrin-bound iron (NTBI), a toxic but less researched pool of circulating iron that is likely to increase due to pathological and/or iatrogenic systemic iron overload. Here, we compared the distribution of radiolabeled-NTBI (59Fe-NTBI) and transferrin-bound iron (59Fe-Tf) in mouse models of iron overload in the absence or presence of inflammation. Following a short pulse, most of the 59Fe-NTBI was taken up by the liver, followed by the kidney, pancreas, and heart...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28549890/-18-f-labeled-indole-based-analogs-as-highly-selective-radioligands-for-imaging-sigma-2-receptors-in-the-brain
#2
Liang Wang, Jiajun Ye, Yingfang He, Winnie Deuther-Conrad, Jinming Zhang, Xiaojun Zhang, Mengchao Cui, Jörg Steinbach, Yiyun Huang, Peter Brust, Hongmei Jia
We have designed and synthesized a series of indole-based σ2 receptor ligands containing 5,6-dimethoxyisoindoline or 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline as pharmacophore. In vitro competition binding assays showed that all ten ligands possessed low nanomolar affinity (Ki=1.79-5.23nM) for σ2 receptors and high subtype selectivity (Ki (σ2)/Ki (σ1)=56-708). Moreover, they showed high selectivity for σ2 receptor over the vesicular acetylcholine transporter (>1000-fold). The corresponding radiotracers [(18)F]16 and [(18)F]21 were prepared by an efficient one-pot, two-step reaction sequence with a home-made automated synthesis module, with 10-15% radiochemical yield and radiochemical purity of >99%...
May 10, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28549591/single-allele-lmbrd1-knockout-results-in-cardiac-hypertrophy
#3
Linda Tzu-Ling Tseng, Chieh-Liang Lin, Kuei-Hsiang Pan, Kai-Yuan Tzen, Ming-Jai Su, Chia-Ti Tsai, Yi-Han Li, Pai-Chi Li, Fu-Tien Chiang, Shin C Chang, Ming-Fu Chang
BACKGROUND/PURPOSE: LMBD1 protein, a type IV-B plasma membrane protein possessing nine putative trans-membrane domains, was previously demonstrated at cellular level to play a critical part in the signaling cascade of insulin receptor through its involvement in regulating clathrin-mediated endocytosis. However, at physiological level, the significance of LMBD1 protein in cardiac development remains unclear. METHODS: To understand the role of Lmbrd1 gene involved in the cardiac function, heterozygous knockout mice were used as an animal model system...
May 23, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28549191/maintenance-of-phosphate-homeostasis-and-root-development-are-coordinately-regulated-by-myb1-an-r2r3-type-myb-transcription-factor-in-rice
#4
Mian Gu, Jun Zhang, Huanhuan Li, Daqian Meng, Ran Li, Xiaoli Dai, Shichao Wang, Wei Liu, Hongye Qu, Guohua Xu
The adaptive responses of plants to phosphate (Pi) starvation stress are fine-tuned by an elaborate regulatory network. In this study, we identified and characterized a novel Pi starvation-responsive gene, MYB1, encoding an R2R3-type transcription factor in rice. MYB1 was transcriptionally induced in leaf sheaths and old leaf blades. It was localized to the nucleus and expressed mainly in vascular tissues. Mutation of MYB1 led to an increase in Pi uptake and accumulation, accompanied by altered expression of a subset of Pi transporters and several genes involved in Pi starvation signaling...
May 26, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28548087/the-distinct-metabolic-phenotype-of-lung-squamous-cell-carcinoma-defines-selective-vulnerability-to-glycolytic-inhibition
#5
Justin Goodwin, Michael L Neugent, Shin Yup Lee, Joshua H Choe, Hyunsung Choi, Dana M R Jenkins, Robin J Ruthenborg, Maddox W Robinson, Ji Yun Jeong, Masaki Wake, Hajime Abe, Norihiko Takeda, Hiroko Endo, Masahiro Inoue, Zhenyu Xuan, Hyuntae Yoo, Min Chen, Jung-Mo Ahn, John D Minna, Kristi L Helke, Pankaj K Singh, David B Shackelford, Jung-Whan Kim
Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28547568/biofertilizers-and-sustainable-agriculture-exploring-arbuscular-mycorrhizal-fungi
#6
REVIEW
Nicholas O Igiehon, Olubukola O Babalola
Worldwide agricultural food production has to double in 2050 so as to feed the global increasing population while reducing dependency on conventional chemical fertilizers plus pesticides. To accomplish this objective, there is the need to explore the several mutualistic interactions between plant roots and rhizosphere microbiome. Biofertilization is the process of boosting the abundance of microorganisms such as arbuscular mycorrhizal fungi (AMF) in the natural plant rhizosphere which depicts a beneficial alternative to chemical fertilization practices...
May 25, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28546582/control-of-amino-acid-transport-coordinates-metabolic-reprogramming-in-t-cell-malignancy
#7
K M Grzes, M Swamy, J L Hukelmann, E Emslie, L V Sinclair, D A Cantrell
This study explores the regulation and importance of System L amino acid transport in a murine model of T cell acute lymphoblastic leukemia (T-ALL) caused by deletion of phosphatase and tensin homologue deleted on chromosome 10 (PTEN). There has been a strong focus on glucose transport in leukemias but the present data show that primary T-ALL cells have increased transport of multiple nutrients. Specifically, increased leucine transport in T-ALL fuels mammalian target of rapamycin complex 1 (mTORC1) activity which then sustains expression of hypoxia inducible factor-1α (HIF1α) and c-Myc; drivers of glucose metabolism in T cells...
May 26, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28546542/low-cesium-rice-mutation-in-ossos2-reduces-radiocesium-in-rice-grains
#8
Satoru Ishikawa, Shimpei Hayashi, Tadashi Abe, Masato Igura, Masato Kuramata, Hachidai Tanikawa, Manaka Iino, Takashi Saito, Yuji Ono, Tetsuya Ishikawa, Shigeto Fujimura, Akitoshi Goto, Hiroki Takagi
In Japan, radiocesium contamination in foods has become of great concern and it is a primary issue to reduce grain radiocesium concentration in rice (Oryza sativa L.). Here, we report a low-cesium rice mutant 1 (lcs1) with the radiocesium concentration in grain about half that in the wild-type cultivar. Genetic analyses revealed that a mutation in OsSOS2, which encodes a serine/threonine-protein kinase required for the salt overly sensitive (SOS) pathway in plants, is responsible for the decreased cesium (Cs) concentrations in lcs1...
May 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28545227/potential-use-of-chemoprotectants-against-the-toxic-effects-of-cyanotoxins-a-review
#9
REVIEW
Remedios Guzmán-Guillén, María Puerto, Daniel Gutiérrez-Praena, Ana I Prieto, Silvia Pichardo, Ángeles Jos, Alexandre Campos, Vitor Vasconcelos, Ana M Cameán
Cyanobacterial toxins, particularly microcystins (MCs) and cylindrospermopsin (CYN), are responsible for toxic effects in humans and wildlife. In order to counteract or prevent their toxicity, various strategies have been followed, such as the potential application of chemoprotectants. A review of the main substances evaluated for this aim, as well as the doses and their influence on cyanotoxin-induced toxicity, has been performed. A search of the literature shows that research on MCs is much more abundant than research on CYN...
May 23, 2017: Toxins
https://www.readbyqxmd.com/read/28545156/the-boron-transporter-bnac4-bor1-1c-is-critical-for-inflorescence-development-and-fertility-under-boron-limitation-in-brassica-napus
#10
Quan Zhang, Haifei Chen, Mingliang He, Zhuqing Zhao, Hongmei Cai, Guangda Ding, Lei Shi, Fangsen Xu
Boron (B) is an essential micronutrient for plants, but the molecular mechanisms underlying the uptake and distribution of B in allotetraploid rapeseed (Brassica napus) are unclear. Here, we identified a B transporter of rapeseed, BnaC4.BOR1;1c, which expressed in shoot nodes and involved in distributing B to the reproductive organs. Transgenic Arabidopsis plants containing a BnaC4.BOR1;1c promoter-driven GUS reporter gene showed strong GUS activity in roots, nodal regions of the shoots and immature floral buds...
May 25, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28545086/cancer-cell-spheroids-are-a-better-screen-for-the-photodynamic-efficiency-of-glycosylated-photosensitizers
#11
Patrícia M R Pereira, Naxhije Berisha, N V S Dinesh K Bhupathiraju, Rosa Fernandes, João P C Tomé, Charles Michael Drain
Photodynamic Therapy (PDT) relies on the use of non-toxic photosensitizers that are locally and selectively activated by light to induce cell death or apoptosis through reactive oxygen species generation. The conjugation of porphyrinoids with sugars that target cancer is increasingly viewed as an effective way to increase the selectivity of PDT. To date, in vitro PDT efficacy is mostly screened using two-dimensional monolayer cultures. Compared to monolayer cultures, three-dimensional spheroid cultures have unique spatial distributions of nutrients, metabolites, oxygen and signalling molecules; therefore better mimic in vivo conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28544973/pegylation-of-a-tlr2-agonist-based-vaccine-delivery-system-improves-antigen-trafficking-and-the-magnitude-of-ensuing-antibody-and-cd8-t-cell-responses
#12
Toshiki Sekiya, Junya Yamagishi, John Henry V Gray, Paul G Whitney, Axel Martinelli, Weiguang Zeng, Chinn Yi Wong, Chihiro Sugimoto, David C Jackson, Brendon Y Chua
The lipopeptide R4Pam2Cys is an agonist for toll-like receptor-2 (TLR2), a key pathogen-associated molecular pattern receptor expressed on many antigen-presenting cells such as dendritic cells (DCs). Electrostatic association of R4Pam2Cys with soluble protein antigens significantly enhances their immunogenicity and there is evidence to suggest that reducing the size of suitably adjuvanted-antigen complexes in solution may further improve their immunostimulatory capabilities. In this study, we investigated how incorporation of polyethylene glycol (PEG) into R4Pam2Cys affects the size, activity and efficacy of formed antigen-lipopeptide complexes...
May 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28544965/nrgd-modified-lycobetaine-and-octreotide-combination-delivery-system-to-overcome-multiple-barriers-and-enhance-anti-glioma-efficacy
#13
Tijia Chen, Xu Song, Ting Gong, Yao Fu, Liuqing Yang, Zhirong Zhang, Tao Gong
For glioma as one of the most common and lethal primary brain tumors, the presence of BBB, BBTB, vasculogenic mimicry (VM) channels and tumor-associated macrophages (TAMs) are key biological barriers. Here, a novel drug delivery system which could efficiently deliver drugs to glioma by overcoming multi-barriers and increase antitumor efficacy through multi-therapeutic mechanisms was well developed. In this study, a multi-target peptide nRGD was used to transport across the BBB, mediate tumor penetration and target TAMs...
May 15, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28544763/hp30-2-a-mitochondrial-prat-protein-for-import-of-signal-sequence-less-precursor-proteins-in-arabidopsis-thaliana
#14
Claudia Rossig, John Gray, Oscar Valdes, Sachin Rustgi, Diter von Wettstein, Christiane Reinbothe, Steffen Reinbothe
Chloroplasts and mitochondria contain a family of putative preprotein and amino acid transporters designated PRAT. Here, we analyzed the role of two previously characterized PRAT protein family member, encoded by At3g49560 (HP30) and At5g24650 (HP30-2), in planta using a combination of genetic, cell biological and biochemical approaches. Expression studies and GFP tagging identified HP30-2 both in chloroplasts and mitochondria, whereas HP30 was located exclusively in chloroplasts. Biochemical evidence was obtained for an association of mitochondrial HP30-2 with two distinct protein complexes, one containing the inner membrane translocase TIM22 and the other containing an alternative NAD(P)H dehydrogenase subunit (NDC1) implicated in a respiratory complex 1-like electron transport chain...
May 22, 2017: Journal of Integrative Plant Biology
https://www.readbyqxmd.com/read/28544656/the-cellular-ceramide-transport-protein-cert-promotes-chlamydia-psittaci-infection-and-controls-bacterial-sphingolipid-uptake
#15
Sophia Koch-Edelmann, Sebastian Banhart, Essa M Saied, Laura Rose, Lukas Aeberhard, Michael Laue, Joerg Doellinger, Christoph Arenz, Dagmar Heuer
Chlamydiaceae are bacterial pathogens that cause diverse diseases in humans and animals. Despite their broad host and tissue tropism, all Chlamydia species share an obligate intracellular cycle of development and have evolved sophisticated mechanisms to interact with their eukaryotic host cells. Here, we have analyzed interactions of the zoonotic pathogen Chlamydia psittaci with a human epithelial cell line. We found that C. psittaci recruits the ceramide transport protein CERT to its inclusion. Chemical inhibition and CRISPR/Cas9-mediated knockout of CERT showed that CERT is a crucial factor for C...
May 19, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28544329/dissolving-microneedle-arrays-for-transdermal-delivery-of-amphiphilic-vaccines
#16
Myunggi An, Haipeng Liu
Amphiphilic vaccine based on lipid-polymer conjugates is a new type of vaccine capable of self-delivering to the immune system. When injected subcutaneously, amphiphilic vaccines efficiently target antigen presenting cells in the lymph nodes (LNs) via a unique albumin-mediated transport and uptake mechanism and induce potent humoral and cellular immune responses. However, whether this new type of vaccine can be administrated via a safe, convenient microneedle-based transdermal approach remains unstudied. For such skin barrier-disruption systems, a simple application of microneedle arrays (MNs) is desired to disrupt the stratum corneum, and for rapid and pain-free self-administration of vaccines into the skin, the anatomic place permeates with an intricate mesh of lymphatic vessels draining to LNs...
May 19, 2017: Small
https://www.readbyqxmd.com/read/28541045/orally-absorbed-cyclic-peptides
#17
Daniel S Nielsen, Nicholas E Shepherd, Weijun Xu, Andrew J Lucke, Martin J Stoermer, David P Fairlie
Peptides and proteins are not orally bioavailable in mammals, although a few peptides are intestinally absorbed in small amounts. Polypeptides are generally too large and polar to passively diffuse through lipid membranes, while most known active transport mechanisms facilitate cell uptake of only very small peptides. Systematic evaluations of peptides with molecular weights above 500 Da are needed to identify parameters that influence oral bioavailability. Here we describe 125 cyclic peptides containing four to thirty-seven amino acids that are orally absorbed by mammals...
May 25, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28540373/in-vitro-cellular-behaviors-and-toxicity-assays-of-small-sized-fluorescent-silicon-nanoparticles
#18
Zhaohui Cao, Fei Peng, Zhilin Hu, Binbin Chu, Yiling Zhong, Yuanyuan Su, Sudan He, Yao He
Extensive investigations have been carried out for evaluating the toxicology of various nanomaterials (e.g., carbon- and metal-based nanomaterials), which offer invaluable information for assessing the feasibility of nanomaterial-based wide-ranging applications. In recent years, sufficient efforts have been made to develop fluorescent small-sized silicon nanoparticles (SiNPs) as a novel optical material simultaneously featuring strong fluorescence and ultrahigh photostability, providing high promise for a myriad of biological, biomedical and electronic applications...
May 25, 2017: Nanoscale
https://www.readbyqxmd.com/read/28540303/identifying-the-genes-responsible-for-iron-limited-condition-in-riemerella-anatipestifer-ch-1-through-rna-seq-based-analysis
#19
MaFeng Liu, Mi Huang, DeKang Zhu, MingShu Wang, RenYong Jia, Shun Chen, KunFeng Sun, Qiao Yang, Ying Wu, Francis Biville, AnChun Cheng
One of the important elements for most bacterial growth is iron, the bioavailability of which is limited in hosts. Riemerella anatipestifer (R. anatipestifer, RA), an important duck pathogen, requires iron to live. However, the genes involved in iron metabolism and the mechanisms of iron transport are largely unknown. Here, we investigated the transcriptomic effects of iron limitation condition on R. anatipestifer CH-1 using the RNA-Seq and RNA-Seq-based analysis. Data analysis revealed genes encoding functions related to iron homeostasis, including a number of putative TonB-dependent receptor systems, a HmuY-like protein-dependent hemin (an iron-containing porphyrin) uptake system, a Feo system, a gene cluster related to starch utilization, and genes encoding hypothetical proteins that were significantly upregulated in response to iron limitation...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28540173/self-microemulsifying-drug-delivery-system-for-improving-the-bioavailability-of-huperzine-a-by-lymphatic-uptake
#20
Fang Li, Rongfeng Hu, Bin Wang, Yun Gui, Gang Cheng, Song Gao, Lei Ye, Jihui Tang
Huperzine A (Hup-A) is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion (SPIP) technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration-time curve (AUC) of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension (P<0...
May 2017: Acta Pharmaceutica Sinica. B
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