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https://www.readbyqxmd.com/read/27913960/neuroimaging-abnormalities-in-clade-c-hiv-are-independent-of-tat-genetic-diversity
#1
Robert H Paul, Sarah Phillips, Jacqueline Hoare, David H Laidlaw, Ryan Cabeen, Gayla R Olbricht, Yuqing Su, Dan J Stein, Susan Engelbrecht, Soraya Seedat, Lauren E Salminen, Laurie M Baker, Jodi Heaps, John Joska
Controversy remains regarding the neurotoxicity of clade C human immunodeficiency virus (HIV-C). When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C Tat protein (C31S) results in less severe brain injury compared to other viral clades. By contrast, patient cohort studies identify significant neuropsychological impairment among HIV-C individuals independent of Tat variability. The present study clarified this discrepancy by examining neuroimaging markers of brain integrity among HIV-C individuals with and without the Tat substitution...
December 2, 2016: Journal of Neurovirology
https://www.readbyqxmd.com/read/27911840/multistep-regulation-of-autophagy-by-wnk1
#2
Sachith Gallolu Kankanamalage, A-Young Lee, Chonlarat Wichaidit, Andres Lorente-Rodriguez, Akansha M Shah, Steve Stippec, Angelique W Whitehurst, Melanie H Cobb
The with-no-lysine (K) (WNK) kinases are an atypical family of protein kinases that regulate ion transport across cell membranes. Mutations that result in their overexpression cause hypertension-related disorders in humans. Of the four mammalian WNKs, only WNK1 is expressed throughout the body. We report that WNK1 inhibits autophagy, an intracellular degradation pathway implicated in several human diseases. Using small-interfering RNA-mediated WNK1 knockdown, we show autophagosome formation and autophagic flux are accelerated...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911709/shuttling-and-sorting-lipid-modified-cargo-into-the-cilia
#3
REVIEW
Louise A Stephen, Shehab Ismail
Primary cilia are hair-like microtubule-based organelles that can be found on almost all human cell types. Although the cilium is not separated from the cell by membranes, their content is different from that of the cell body and their membrane composition is distinct from that of the plasma membrane. Here, we will introduce a molecular machinery that shuttles and sorts lipid-modified proteins to the cilium, thus contributing in maintaining its distinct composition. The mechanism involves the binding of the GDI-like solubilising factors, uncoordinated (UNC)119a, UNC119b and PDE6D, to the lipid-modified ciliary cargo and the specific release of the cargo in the cilia by the ciliary small G-protein Arl3 in a GTP-dependent manner...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27910960/unc-5-homolog-b-unc5b-is-one-of-the-key-downstream-targets-of-n-%C3%AE-acetyltransferase-10-naa10
#4
Huiyu Xu, Yong Han, Bing Liu, Rong Li
N-α-acetyltransferase 10 (Naa10) displays alpha (N-terminal) acetyltransferase activity. It functions as a major modulator of cell growth and differentiation. Until now, a few downstream targets were found, but no studies have concerned about which gene is the early event of Naa10 downstream target. As we know, the earlier events may play more significant role in Naa10 pathway. Through construction of Naa10 stably knocked down H1299 cell line, we discovered cell morphological changes induced by Naa10. Moreover, potential function of Naa10 in cell morphogenesis was also indicated using cDNA microarray analysis of the Naa10 stably knock-down cell line...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27903405/separation-of-44-ti-from-proton-irradiated-scandium-by-using-solid-phase-extraction-chromatography-and-design-of-44-ti-44-sc-generator-system
#5
V Radchenko, C A L Meyer, J W Engle, C M Naranjo, G A Unc, T Mastren, M Brugh, E R Birnbaum, K D John, F M Nortier, M E Fassbender
Scandium-44g (half-life 3.97h [1]) shows promise for positron emission tomography (PET) imaging of longer biological processes than that of the current gold standard, (18)F, due to its favorable decay parameters. One source of (44g)Sc is the long-lived parent nuclide (44)Ti (half-life 60.0 a). A (44)Ti/(44g)Sc generator would have the ability to provide radionuclidically pure (44g)Sc on a daily basis. The production of (44)Ti via the (45)Sc(p,2n) reaction requires high proton beam currents and long irradiation times...
November 24, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/27903333/diffusion-tensor-imaging-predictors-of-episodic-memory-decline-in-healthy-elders-at-genetic-risk-for-alzheimer-s-disease
#6
Melissa A Lancaster, Michael Seidenberg, J Carson Smith, Kristy A Nielson, John L Woodard, Sally Durgerian, Stephen M Rao
OBJECTIVES: White matter (WM) integrity within the mesial temporal lobe (MTL) is important for episodic memory (EM) functioning. The current study investigated the ability of diffusion tensor imaging (DTI) in MTL WM tracts to predict 3-year changes in EM performance in healthy elders at disproportionately higher genetic risk for Alzheimer's disease (AD). METHODS: Fifty-one cognitively intact elders (52% with family history (FH) of dementia and 33% possessing an Apolipoprotein E ε4 allelle) were administered the Rey Auditory Verbal Learning Test (RAVLT) at study entry and at 3-year follow-up...
November 2016: Journal of the International Neuropsychological Society: JINS
https://www.readbyqxmd.com/read/27903295/prevalence-and-risk-factors-of-periodontal-disease-among-pre-conception-chinese-women
#7
Hong Jiang, Yi Su, Xu Xiong, Emily Harville, Hongqiao Wu, Zhijun Jiang, Xu Qian
BACKGROUND: Periodontal disease is one of the most common chronic infectious diseases. It has been reported that periodontal disease is associated with various adverse pregnancy outcomes including preterm birth, low birth weight, and gestational diabetes mellitus. Given the fact that the treatment for periodontal disease during pregnancy was ineffective in improving pregnancy outcomes by most of studies, the pre-conception period has been put forward as a more optimal time. However, very few studies have reported the prevalence of periodontal disease among pre-conception women...
December 1, 2016: Reproductive Health
https://www.readbyqxmd.com/read/27887947/berberine-enhances-the-ampk-activation-and-autophagy-and-mitigates-high-glucose-induced-apoptosis-of-mouse-podocytes
#8
Yingli Jin, Shuping Liu, Qingshan Ma, Dong Xiao, Li Chen
High glucose concentration can induce injury of podocytes and berberine has a potent activity against diabetic nephropathy. However, whether and how berberine can inhibit high glucose-mediated injury of podocytes have not been clarified. This study tested the effect of berberine on high glucose-mediated apoptosis and the AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) activation and autophagy in podocytes. The results indicated that berberine significantly mitigated high glucose-decreased cell viability, and nephrin and podocin expression as well as apoptosis in mouse podocytes...
November 22, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27879319/amp-activated-kinase-ampk-promotes-innate-immunity-and-antiviral-defense-through-modulation-of-stimulator-of-interferon-genes-sting-signaling
#9
Daniel Prantner, Darren J Perkins, Stefanie N Vogel
The host protein Stimulator of Interferon Genes (STING) has been shown to be essential for recognition of both viral and intracellular bacterial pathogens, but its regulation remains unclear. Previously, we reported that mitochondrial membrane potential regulates STING-dependent IFN-beta induction independently of ATP synthesis. Since mitochondrial membrane potential controls calcium homeostasis, and AMP-activated protein kinase (AMPK) is regulated, in part, by intracellular calcium, we postulated that AMPK participates in STING activation; however, its role has yet to be been defined...
November 22, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27877110/forward-genetic-screen-in-caenorhabditis-elegans-suggests-f57a10-2-and-acp-4-as-suppressors-of-c9orf72-related-phenotypes
#10
Xin Wang, Limin Hao, Taixiang Saur, Katelyn Joyal, Ying Zhao, Desheng Zhai, Jie Li, Mochtar Pribadi, Giovanni Coppola, Bruce M Cohen, Edgar A Buttner
An abnormally expanded GGGGCC repeat in C9ORF72 is the most frequent causal mutation associated with amyotrophic lateral sclerosis (ALS)/frontotemporal lobar degeneration (FTLD). Both gain-of-function (gf) and loss-of-function (lf) mechanisms have been involved in C9ORF72 related ALS/FTLD. The gf mechanism of C9ORF72 has been studied in various animal models but not in C. elegans. In the present study, we described mutant C9ORF72 modeling in C. elegans and report the finding of two suppressor genes. We made transgenes containing 9 or 29 repeats of GGGGCC in C9ORF72, driven by either the hsp-16 promoters or the unc-119 promoter...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27875637/ambra1-a-novel-%C3%AE-synuclein-binding-protein-is-implicated-in-the-pathogenesis-of-multiple-system-atrophy
#11
Yasuo Miki, Kunikazu Tanji, Fumiaki Mori, Yota Tatara, Jun Utsumi, Hidenao Sasaki, Akiyoshi Kakita, Hitoshi Takahashi, Gian Maria Fimia, Koichi Wakabayashi
The accumulation of abnormal α-synuclein is the major histopathological feature of Lewy body disease and multiple system atrophy (MSA), which are referred to as synucleinopathies. Although the pathomechanisms underlying synucleinopathies are still unknown, mounting evidence indicates that cytoplasmic degradation systems, such as the autophagy-lysosome and proteasome pathways, are strongly involved in their pathogenesis. Autophagy is tightly regulated by several upstream proteins including UNC-51-like kinase 1/2, beclin1, vacuolar protein sorting-associated protein 34, and autophagy/beclin1 regulator 1 (AMBRA1)...
November 22, 2016: Brain Pathology
https://www.readbyqxmd.com/read/27873163/an-update-on-the-use-of-immunomodulators-in-primary-immunodeficiencies
#12
REVIEW
Pandiarajan Vignesh, Amit Rawat, Surjit Singh
The genomic revolution in the past decade fuelled by breathtaking advances in sequencing technologies has defined several new genetic diseases of the immune system. Many of these newly characterized diseases are a result of defects in genes involved in immune regulation. The discovery of these diseases has opened a vista of new therapeutic possibilities. Immunomodulatory agents, a hitherto unexplored therapeutic option in primary immunodeficiency diseases have been tried in a host of these newly described maladies...
November 21, 2016: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/27869123/a-systems-study-reveals-concurrent-activation-of-ampk-and-mtor-by-amino-acids
#13
Piero Dalle Pezze, Stefanie Ruf, Annika G Sonntag, Miriam Langelaar-Makkinje, Philip Hall, Alexander M Heberle, Patricia Razquin Navas, Karen van Eunen, Regine C Tölle, Jennifer J Schwarz, Heike Wiese, Bettina Warscheid, Jana Deitersen, Björn Stork, Erik Fäßler, Sascha Schäuble, Udo Hahn, Peter Horvatovich, Daryl P Shanley, Kathrin Thedieck
Amino acids (aa) are not only building blocks for proteins, but also signalling molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a key mediator. However, little is known about whether aa, independently of mTORC1, activate other kinases of the mTOR signalling network. To delineate aa-stimulated mTOR network dynamics, we here combine a computational-experimental approach with text mining-enhanced quantitative proteomics. We report that AMP-activated protein kinase (AMPK), phosphatidylinositide 3-kinase (PI3K) and mTOR complex 2 (mTORC2) are acutely activated by aa-readdition in an mTORC1-independent manner...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27859879/association-between-social-support-functional-status-and-change-in-health-related-quality-of-life-and-changes-in-anxiety-and-depression-in-colorectal-cancer-patients
#14
REVIEW
M Gonzalez-Saenz de Tejada, A Bilbao, M Baré, E Briones, C Sarasqueta, J M Quintana, A Escobar
OBJECTIVE: The aim of this study was to explore the association between baseline social support, functional status and change in HRQoL in colorectal cancer patients and change in anxiety and depression measured by HADS at one year post-surgery. METHODS: Consecutive patients who were due to undergo therapeutic surgery for the first time for colon or rectal cancer in nine hospitals in Spain were eligible for the study. Patients completed the following questionnaires prior to surgery and 12 months afterwards: one HRQoL instrument, the EORTC QLQ-C30; a social support questionnaire, the Duke-UNC Functional Social Support Questionnaire; the Barthel Index, to assess functional status; the Hospital Anxiety and Depression Scale (HADS), to assess anxiety and depression; as well as questions about sociodemographic information...
November 8, 2016: Psycho-oncology
https://www.readbyqxmd.com/read/27855782/neuroendocrine-modulation-sustains-the-c-elegans-forward-motor-state
#15
Maria A Lim, Jyothsna Chitturi, Valeriya Laskova, Jun Meng, Daniel Findeis, Anne Wiekenberg, Ben Mulcahy, Linjiao Luo, Yan Li, Yangning Lu, Wesley Hung, Yixin Qu, Chi-Yip Ho, Douglas Holmyard, Ni Ji, Rebecca McWhirter, Aravinthan Dt Samuel, David M Miller, Ralf Schnabel, John A Calarco, Mei Zhen
Neuromodulators shape neural circuit dynamics. Combining electron microscopy, genetics, transcriptome profiling, calcium imaging, and optogenetics, we discovered a peptidergic neuron that modulates C. elegans motor circuit dynamics. The Six/SO-family homeobox transcription factor UNC-39 governs lineage-specific neurogenesis to give rise to a neuron RID. RID bears the anatomic hallmarks of a specialized endocrine neuron: it harbors near-exclusive dense core vesicles that cluster periodically along the axon, and expresses multiple neuropeptides, including the FMRF-amide-related FLP-14...
November 18, 2016: ELife
https://www.readbyqxmd.com/read/27846372/loss-of-ulk1-increases-rps6kb1-ncor1-repression-of-nr1h-lxr-mediated-scd1-transcription-and-augments-lipotoxicity-in-hepatic-cells
#16
Rohit Anthony Sinha, Brijesh K Singh, Jin Zhou, Sherwin Xie, Benjamin L Farah, Ronny Lesmana, Kenji Ohba, Madhulika Tripathi, Sujoy Ghosh, Anthony N Hollenberg, Paul M Yen
Lipotoxicity caused by saturated fatty acids (SFAs) induces tissue damage and inflammation in metabolic disorders. SCD1 (stearoyl-Coenzyme A desaturase 1) converts SFAs to mono-unsaturated fatty acids (MUFAs) that are incorporated into triglycerides and stored in lipid droplets. SCD1 thus helps protect hepatocytes from lipotoxicity and its reduced expression is associated with increased lipotoxic injury in cultured hepatic cells and mouse models. To further understand the role of SCD1 in lipotoxicity, we examined the regulation of Scd1 in hepatic cells treated with palmitate, and found that NR1H/LXR (nuclear receptor subfamily 1 group H) ligand, GW3965, induced Scd1 expression and lipid droplet formation to improve cell survival...
November 15, 2016: Autophagy
https://www.readbyqxmd.com/read/27783190/a-novel-tetra-primer-arms-pcr-based-assay-for-genotyping-snp-rs12303764-g-t-of-human-unc-51-like-kinase-1-gene
#17
Rohit Randhawa, Ajay Duseja, Harish Changotra
Various case-control studies have shown association of single nucleotide polymorphism rs12303764(G/T) in ULK1 with crohn's disease. The techniques used in these studies were time consuming, complicated and require sophisticated/expensive instruments. Therefore, in order to overcome these problems, we have developed a new, rapid and cost effective Tetra-primer ARMS-PCR assay to genotype single nucleotide polymorphism rs12303764(G/T) of ULK1 gene. We manually designed allele specific primers. DNA fragment amplified using outer primers was sequenced to obtain samples with known genotypes (GG, GT and TT) for further use in the development of T-ARMS-PCR assay...
October 25, 2016: Molecular Biology Reports
https://www.readbyqxmd.com/read/27777636/maternal-vitamin-d-depletion-alters-dna-methylation-at-imprinted-loci-in-multiple-generations
#18
Jing Xue, Sarah A Schoenrock, William Valdar, Lisa M Tarantino, Folami Y Ideraabdullah
BACKGROUND: Environmental perturbation of epigenetic mechanisms is linked to a growing number of diseases. Characterizing the role environmental factors play in modifying the epigenome is important for disease etiology. Vitamin D is an essential nutrient affecting brain, bone, heart, immune and reproductive health. Vitamin D insufficiency is a global issue, and the role in maternal and child health remains under investigation. METHODS: We used Collaborative Cross (CC) inbred mice to characterize the effect of maternal vitamin D depletion on offspring phenotypic and epigenetic outcomes at imprinted domains (H19/Igf2, Snrpn, Dlk1/Gtl2, and Grb10) in the soma (liver) and germline (sperm)...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27774051/c9orf72-s-interaction-with-rab-gtpases-modulation-of-membrane-traffic-and-autophagy
#19
Bor L Tang
Hexanucleotide repeat expansion in an intron of Chromosome 9 open reading frame 72 (C9orf72) is the most common genetic cause of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). While functional haploinsufficiency of C9orf72 resulting from the mutation may play a role in ALS/FTD, the actual cellular role of the protein has been unclear. Recent findings have now shown that C9orf72 physically and functionally interacts with multiple members of the Rab small GTPases family, consequently exerting important influences on cellular membrane traffic and the process of autophagy...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27760755/ca2-permeability-and-na-conductance-in-cellular-toxicity-caused-by-hyperactive-deg-enac-channels
#20
Cristina Matthewman, Tyne W Miller-Fleming, David M Miller, Laura Bianchi
Hyperactivated DEG/ENaC channels cause neuronal death mediated by intracellular Ca(2+) overload. Mammalian ASIC1a channels and MEC-4(d) neurotoxic channels in Caenorhabditis elegans both conduct Na(+) and Ca(2+), raising the possibility that direct Ca(2+) influx through these channels contributes to intracellular Ca(2+) overload. However, we showed that the homologous C. elegans DEG/ENaC channel UNC-8(d) is not Ca(2+) permeable, yet it is neurotoxic, suggesting that Na(+) influx is sufficient to induce cell death...
December 1, 2016: American Journal of Physiology. Cell Physiology
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