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https://www.readbyqxmd.com/read/29166751/is-there-a-glucose-metabolic-signature-of-spreading-tdp-43-pathology-in-amyotrophic-lateral-sclerosis
#1
Donatienne van Weehaeghe, Jenny Ceccarini, Stefanie M Willekens, Joke de Vocht, Philip van Damme, Koen van Laere
BACKGROUND: Recently, four neuropathological stages of amyotrophic lateral sclerosis (ALS) with spreading of transactive response DNA-Binding Protein-43 pathology were described. Although 18F-FDG PET has been useful in diagnosis and prognosis of ALS patients, in vivo disease staging using glucose metabolic patterns across the different ALS stages have not been attempted so far. In this study, we investigated whether the discriminant brain regions of the neuropathological stage model can be translated to metabolic patterns for in vivo staging of ALS...
November 22, 2017: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29166729/-use-dependence-and-reverse-use-dependence-of-antiarrhythmic-drugs
#2
W P Zhao, Y Gao, T Liu
No abstract text is available yet for this article.
November 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/29166700/dlp1-dependent-mitochondrial-fragmentation-and-redistribution-mediate-prion-associated-mitochondrial-dysfunction-and-neuronal-death
#3
Chaosi Li, Di Wang, Wei Wu, Wei Yang, Syed Zahid Ali Shah, Ying Zhao, Yuhan Duan, Lu Wang, Xiangmei Zhou, Deming Zhao, Lifeng Yang
Mitochondrial malfunction is a universal and critical step in the pathogenesis of many neurodegenerative diseases including prion diseases. Dynamin-like protein 1 (DLP1) is one of the key regulators of mitochondrial fission. In this study, we investigated the role of DLP1 in mitochondrial fragmentation and dysfunction in neurons using in vitro and in vivo prion disease models. Mitochondria became fragmented and redistributed from axons to soma, correlated with increased mitochondrial DLP1 expression in murine primary neurons (N2a cells) treated with the prion peptide PrP(106-126) in vitro as well as in prion strain-infected hamster brain in vivo...
November 22, 2017: Aging Cell
https://www.readbyqxmd.com/read/29166668/interleukin-36%C3%AE-and-il-36-receptor-signaling-mediate-impaired-host-immunity-and-lung-injury-in-cytotoxic-pseudomonas-aeruginosa-pulmonary-infection-role-of-prostaglandin-e2
#4
Tetsuji Aoyagi, Michael W Newstead, Xianying Zeng, Yuta Nanjo, Marc Peters-Golden, Mitsuo Kaku, Theodore J Standiford
Pseudomonas aeruginosa is a Gram-negative pathogen that can lead to severe infection associated with lung injury and high mortality. The interleukin (IL)-36 cytokines (IL-36α, IL-36β and IL-36γ) are newly described IL-1 like family cytokines that promote inflammatory response via binding to the IL-36 receptor (IL-36R). Here we investigated the functional role of IL-36 cytokines in the modulating of innate immune response against P. aeruginosa pulmonary infection. The intratracheal administration of flagellated cytotoxic P...
November 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29166663/a-general-model-for-predicting-the-binding-affinity-of-reversibly-and-irreversibly-dimerized-ligands
#5
Kenneth W Foreman
Empirical data has shown that bivalent inhibitors can bind a given target protein significantly better than their monomeric counterparts. However, predicting the corresponding theoretical fold improvements has been challenging. The current work builds off the reacted-site probability approach to provide a straightforward baseline reference model for predicting fold-improvements in effective affinity of dimerized ligands over their monomeric counterparts. For the more familiar irreversibly linked bivalents, the model predicts a weak dependence on tether length and a scaling of the effective affinity with the 3/2 power of the monomer's affinity...
2017: PloS One
https://www.readbyqxmd.com/read/29166655/how-well-do-you-know-your-mutation-complex-effects-of-genetic-background-on-expressivity-complementation-and-ordering-of-allelic-effects
#6
Christopher H Chandler, Sudarshan Chari, Alycia Kowalski, Lin Choi, David Tack, Michael DeNieu, William Pitchers, Anne Sonnenschein, Leslie Marvin, Kristen Hummel, Christian Marier, Andrew Victory, Cody Porter, Anna Mammel, Julie Holms, Gayatri Sivaratnam, Ian Dworkin
For a given gene, different mutations influence organismal phenotypes to varying degrees. However, the expressivity of these variants not only depends on the DNA lesion associated with the mutation, but also on factors including the genetic background and rearing environment. The degree to which these factors influence related alleles, genes, or pathways similarly, and whether similar developmental mechanisms underlie variation in the expressivity of a single allele across conditions and among alleles is poorly understood...
November 22, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29166650/feeding-induced-changes-in-allatostatin-a-and-short-neuropeptide-f-in-the-antennal-lobes-affect-odor-mediated-host-seeking-in-the-yellow-fever-mosquito-aedes-aegypti
#7
Peter Christ, Anna Reifenrath, Jörg Kahnt, Frank Hauser, Sharon Rose Hill, Joachim Schachtner, Rickard Ignell
Aedes aegypti is a model species in which the endogenous regulation of odor-mediated host seeking behavior has received some attention. Sugar feeding and host seeking in female A. aegypti are transiently inhibited following a blood meal. This inhibition is partially mediated by short neuropeptide F (sNPF). The paired antennal lobes (ALs), as the first processing centers for olfactory information, has been shown to play a significant role in the neuropeptidergic regulation of odor-mediated behaviors in insects...
2017: PloS One
https://www.readbyqxmd.com/read/29166628/biochar-application-for-the-remediation-of-heavy-metal-polluted-land-a-review-of-in-situ-field-trials
#8
David O'Connor, Tianyue Peng, Junli Zhang, Daniel C W Tsang, Daniel S Alessi, Zhengtao Shen, Nanthi S Bolan, Deyi Hou
Polluted land is a global issue, especially for developing countries. It has been reported that soil amendment with biochar may reduce the bioavailability of a wide range of contaminants, including heavy metal(loids), potentially reclaiming contaminated soils for agricultural use. However, there have been only limited reports on the in situ application of biochar at the field scale. This review was devoted to providing preliminary scientific evidence from these field trials, based on a review of 29 publications involving field applications of biochar in 8 different countries...
November 19, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29166624/impact-of-processing-methods-on-the-dissolution-of-artemether-from-two-non-ordered-mesoporous-silicas
#9
Hira Tahir, Yasser Shahzad, Laura J Waters, Talib Hussain, Abid Mehmood Yousaf, Tariq Mahmood, Rizwan Sheikh
Poor aqueous solubility is often linked with a poor dissolution rate and ultimately, limited bioavailability of pharmaceutical compounds. This study describes the application of mesoporous materials (Syloid 244 and Syloid AL1) in improving the dissolution rate of a drug with poor aqueous solubility, namely artemether, utilising different processing methods including physical mixing, co-grinding and solid dispersions prepared by solvent evaporation and the lyophilisation technique. The prepared formulations were extensively characterised for their solid-state properties and the drug release attributes were studied...
November 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29166620/a-cell-line-specific-atlas-of-parp-mediated-protein-asp-glu-adp-ribosylation-in-breast-cancer
#10
Yuanli Zhen, Yajie Zhang, Yonghao Yu
PARP1 plays a critical role in regulating many biological processes linked to cellular stress responses. Although DNA strand breaks are potent stimuli of PARP1 enzymatic activity, the context-dependent mechanism regulating PARP1 activation and signaling is poorly understood. We performed global characterization of the PARP1-dependent, Asp/Glu-ADP-ribosylated proteome in a panel of cell lines originating from benign breast epithelial cells, as well as common subtypes of breast cancer. From these analyses, we identified 503 specific ADP-ribosylation sites on 322 proteins...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166617/spatiotemporal-proteomic-profiling-of-huntington-s-disease-inclusions-reveals-widespread-loss-of-protein-function
#11
Fabian Hosp, Sara Gutiérrez-Ángel, Martin H Schaefer, Jürgen Cox, Felix Meissner, Mark S Hipp, F-Ulrich Hartl, Rüdiger Klein, Irina Dudanova, Matthias Mann
Aggregation of polyglutamine-expanded huntingtin exon 1 (HttEx1) in Huntington's disease (HD) proceeds from soluble oligomers to late-stage inclusions. The nature of the aggregates and how they lead to neuronal dysfunction is not well understood. We employed mass spectrometry (MS)-based quantitative proteomics to dissect spatiotemporal mechanisms of neurodegeneration using the R6/2 mouse model of HD. Extensive remodeling of the soluble brain proteome correlated with insoluble aggregate formation during disease progression...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166615/olfactory-experience-and-developmental-stage-dependent-control-of-cpeb4-regulates-c-fos-mrna-translation-for-granule-cell-survival
#12
Ching-San Tseng, Hsu-Wen Chao, Hsien-Sung Huang, Yi-Shuian Huang
Mammalian olfactory bulbs (OBs) require continuous replenishment of interneurons (mainly granule cells [GCs]) to support local circuits throughout life. Two spatiotemporally distinct waves of postnatal neurogenesis contribute to expanding and maintaining the GC pool. Although neonate-born GCs have a higher survival rate than adult-born GCs, the molecular mechanism underlying this survival remains unclear. Here, we find that cytoplasmic polyadenylation element-binding protein 4 (CPEB4) acts as a survival factor exclusively for early postnatal GCs...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166608/s-nitrosylation-of-pink1-attenuates-pink1-parkin-dependent-mitophagy-in-hipsc-based-parkinson-s-disease-models
#13
Chang-Ki Oh, Abdullah Sultan, Joseph Platzer, Nima Dolatabadi, Frank Soldner, Daniel B McClatchy, Jolene K Diedrich, John R Yates, Rajesh Ambasudhan, Tomohiro Nakamura, Rudolf Jaenisch, Stuart A Lipton
Mutations in PARK6 (PINK1) and PARK2 (Parkin) are linked to rare familial cases of Parkinson's disease (PD). Mutations in these genes result in pathological dysregulation of mitophagy, contributing to neurodegeneration. Here, we report that environmental factors causing a specific posttranslational modification on PINK1 can mimic these genetic mutations. We describe a molecular mechanism for impairment of mitophagy via formation of S-nitrosylated PINK1 (SNO-PINK1). Mitochondrial insults simulating age- or environmental-related stress lead to increased SNO-PINK1, inhibiting its kinase activity...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166607/kdm2b-regulates-somatic-reprogramming-through-variant-prc1-complex-dependent-function
#14
Zhiwei Zhou, Xuejie Yang, Jiangping He, Jing Liu, Fang Wu, Shengyong Yu, Yuting Liu, Runxia Lin, He Liu, Yuanbin Cui, Chunhua Zhou, Xiaoshan Wang, Jian Wu, Shangtao Cao, Lin Guo, Lihui Lin, Tao Wang, Xiaozhong Peng, Boqing Qiang, Andrew P Hutchins, Duanqing Pei, Jiekai Chen
Polycomb repressive complex 1 (PRC1) plays essential roles in cell-fate determination. Recent studies have found that the composition of mammalian PRC1 is particularly varied and complex; however, little is known about the functional consequences of these variant PRC1 complexes on cell-fate determination. Here, we show that Kdm2b promotes Oct4-induced somatic reprogramming through recruitment of a variant PRC1 complex (PRC1.1) to CpG islands (CGIs). Furthermore, we find that bone morphogenetic protein (BMP) represses Oct4/Kdm2b-induced somatic reprogramming selectively...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166605/l-type-voltage-gated-ca-2-channels-regulate-synaptic-activity-triggered-recycling-endosome-fusion-in-neuronal-dendrites
#15
Brian G Hiester, Ashley M Bourke, Brooke L Sinnen, Sarah G Cook, Emily S Gibson, Katharine R Smith, Matthew J Kennedy
The repertoire and abundance of proteins displayed on the surface of neuronal dendrites are tuned by regulated fusion of recycling endosomes (REs) with the dendritic plasma membrane. While this process is critical for neuronal function and plasticity, how synaptic activity drives RE fusion remains unexplored. We demonstrate a multistep fusion mechanism that requires Ca(2+) from distinct sources. NMDA receptor Ca(2+) initiates RE fusion with the plasma membrane, while L-type voltage-gated Ca(2+) channels (L-VGCCs) regulate whether fused REs collapse into the membrane or reform without transferring their cargo to the cell surface...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166604/capture-of-dense-core-vesicles-at-synapses-by-jnk-dependent-phosphorylation-of-synaptotagmin-4
#16
Vinita Bharat, Michael Siebrecht, Katja Burk, Saheeb Ahmed, Carsten Reissner, Mahdokht Kohansal-Nodehi, Vicky Steubler, Markus Zweckstetter, Jonathan T Ting, Camin Dean
Delivery of neurotrophins and neuropeptides via long-range trafficking of dense core vesicles (DCVs) from the cell soma to nerve terminals is essential for synapse modulation and circuit function. But the mechanism by which transiting DCVs are captured at specific sites is unknown. Here, we discovered that Synaptotagmin-4 (Syt4) regulates the capture and spatial distribution of DCVs in hippocampal neurons. We found that DCVs are highly mobile and undergo long-range translocation but switch directions only at the distal ends of axons, revealing a circular trafficking pattern...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166603/caveolin1-is-required-for-th1-cell-infiltration-but-not-tight-junction-remodeling-at-the-blood-brain-barrier-in-autoimmune-neuroinflammation
#17
Sarah E Lutz, Julian R Smith, Dae Hwan Kim, Carl V L Olson, Kyle Ellefsen, Jennifer M Bates, Sunil P Gandhi, Dritan Agalliu
Lymphocytes cross vascular boundaries via either disrupted tight junctions (TJs) or caveolae to induce tissue inflammation. In the CNS, Th17 lymphocytes cross the blood-brain barrier (BBB) before Th1 cells; yet this differential crossing is poorly understood. We have used intravital two-photon imaging of the spinal cord in wild-type and caveolae-deficient mice with fluorescently labeled endothelial tight junctions to determine how tight junction remodeling and caveolae regulate CNS entry of lymphocytes during the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166596/the-gcn2-atf4-signaling-pathway-induces-4e-bp-to-bias-translation-and-boost-antimicrobial-peptide-synthesis-in-response-to-bacterial-infection
#18
Deepika Vasudevan, Nicholas K Clark, Jessica Sam, Victoria C Cotham, Beatrix Ueberheide, Michael T Marr, Hyung Don Ryoo
Bacterial infection often leads to suppression of mRNA translation, but hosts are nonetheless able to express immune response genes through as yet unknown mechanisms. Here, we use a Drosophila model to demonstrate that antimicrobial peptide (AMP) production during infection is paradoxically stimulated by the inhibitor of cap-dependent translation, 4E-BP (eIF4E-binding protein; encoded by the Thor gene). We found that 4E-BP is induced upon infection with pathogenic bacteria by the stress-response transcription factor ATF4 and its upstream kinase, GCN2...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166591/a-cd103-conventional-dendritic-cell-surveillance-system-prevents-development-of-overt-heart-failure-during-subclinical-viral-myocarditis
#19
Xavier Clemente-Casares, Siyavash Hosseinzadeh, Iulia Barbu, Sarah A Dick, Jillian A Macklin, Yiming Wang, Abdul Momen, Crystal Kantores, Laura Aronoff, Maylis Farno, Tiffany M Lucas, Joan Avery, Dorrin Zarrin-Khat, Heidi J Elsaesser, Babak Razani, Kory J Lavine, Mansoor Husain, David G Brooks, Clinton S Robbins, Myron Cybulsky, Slava Epelman
Innate and adaptive immune cells modulate heart failure pathogenesis during viral myocarditis, yet their identities and functions remain poorly defined. We utilized a combination of genetic fate mapping, parabiotic, transcriptional, and functional analyses and demonstrated that the heart contained two major conventional dendritic cell (cDC) subsets, CD103(+) and CD11b(+), which differentially relied on local proliferation and precursor recruitment to maintain their tissue residency. Following viral infection of the myocardium, cDCs accumulated in the heart coincident with monocyte infiltration and loss of resident reparative embryonic-derived cardiac macrophages...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166588/regulatory-t-cell-migration-is-dependent-on-glucokinase-mediated-glycolysis
#20
Madhav Kishore, Kenneth C P Cheung, Hongmei Fu, Fabrizia Bonacina, Guosu Wang, David Coe, Eleanor J Ward, Alessandra Colamatteo, Maryam Jangani, Andrea Baragetti, Giuseppe Matarese, David M Smith, Robert Haas, Claudio Mauro, David C Wraith, Klaus Okkenhaug, Alberico L Catapano, Veronica De Rosa, Giuseppe D Norata, Federica M Marelli-Berg
Migration of activated regulatory T (Treg) cells to inflamed tissue is crucial for their immune-modulatory function. While metabolic reprogramming during Treg cell differentiation has been extensively studied, the bioenergetics of Treg cell trafficking remains undefined. We have investigated the metabolic demands of migrating Treg cells in vitro and in vivo. We show that glycolysis was instrumental for their migration and was initiated by pro-migratory stimuli via a PI3K-mTORC2-mediated pathway culminating in induction of the enzyme glucokinase (GCK)...
November 21, 2017: Immunity
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