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https://www.readbyqxmd.com/read/27911022/membrane-defects-and-genetic-redundancy-are-we-at-a-turning-point-for-dyt1-dystonia
#1
REVIEW
Ana Cascalho, Julie Jacquemyn, Rose E Goodchild
Heterozygosity for a 3-base pair deletion (ΔGAG) in TOR1A/torsinA is one of the most common causes of hereditary dystonia. In this review, we highlight current understanding of how this mutation causes disease from research spanning structural biochemistry, cell science, neurobiology, and several model organisms. We now know that homozygosity for ΔGAG has the same effects as Tor1a(KO) , implicating a partial loss of function mechanism in the ΔGAG/+ disease state. In addition, torsinA loss specifically affects neurons in mice, even though the gene is broadly expressed, apparently because of differential expression of homologous torsinB...
December 2, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27909964/oxidative-stress-and-biochemical-markers-of-endothelial-dysfunction-and-organ-damage-under-conditions-of-experimental-nonferrous-metal-intoxication
#2
F S Dzugkoeva, I V Mozhaeva, S G Dzugkoev, O I Margieva, A I Tedtoeva, M A Otiev
Chronic nickel intoxication caused by parenteral nickel chloride administration (0.5 mg/kg of body weight) to Wistar rats led to ROS generation inducing LPO in erythrocyte membranes and homogenates of renal, liver, and myocardial tissue. Superoxide dismutase (SOD) activity was inhibited, while catalase activity and ceruloplasmin concentration increased. LPO and its products disrupted nitric oxide production and reduced its bioavailability, which led to the development of endothelial dysfunction and impaired microcirculatory hemodynamics...
December 2, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27909949/organ-specific-effects-of-low-dose-zinc-pre-exposure-on-high-dose-zinc-induced-mitochondrial-dysfunction-in-large-yellow-croaker-pseudosciaena-crocea
#3
Jia-Lang Zheng, Shuang-Shuang Yuan, Bin Shen, Chang-Wen Wu
The study was carried out to evaluate the effects of low-dose zinc (Zn) pre-exposure on survival rate, new Zn accumulation, and mitochondrial bioenergetics in the liver and spleen of large yellow croaker exposed to high-dose Zn. To the end, fish were pre-exposed to 0 and 2 mg L(-1) Zn for 48 h and post-exposed to 0 and 12 mg L(-1) Zn for 48 h. Twelve milligrams Zn per liter exposure alone reduced survival rate, but the effect did not appear in the 2 mg L(-1) Zn pre-exposure groups. Two milligrams per liter Zn pre-exposure also ameliorated 12 mg Zn L(-1) induced new Zn accumulation, reactive oxygen species (ROS) levels, and mitochondrial swelling in the liver...
December 1, 2016: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/27909897/nha2-is-expressed-in-distal-nephron-and-regulated-by-dietary-sodium
#4
Kalyan C Kondapalli, R Todd Alexander, Jennifer L Pluznick, Rajini Rao
Increased renal reabsorption of sodium is a significant risk factor in hypertension. An established clinical marker for essential hypertension is elevated sodium lithium countertransport (SLC) activity. NHA2 is a newly identified Na(+)(Li(+))/H(+) antiporter with potential genetic links to hypertension, which has been shown to mediate SLC activity and H(+)-coupled Na(+)(Li(+)) efflux in kidney-derived MDCK cells. To evaluate a putative role in sodium homeostasis, we determined the effect of dietary salt on NHA2...
December 1, 2016: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/27907157/human-bone-derived-collagen-for-the-development-of-an-artificial-corneal-endothelial-graft-in-vivo-results-in-a-rabbit-model
#5
Natalia Vázquez, Manuel Chacón, Carlos A Rodríguez-Barrientos, Jesús Merayo-Lloves, Miguel Naveiras, Begoña Baamonde, Jose F Alfonso, Iriana Zambrano-Andazol, Ana C Riestra, Álvaro Meana
Corneal keratoplasty (penetrating or lamellar) using cadaveric human tissue, is nowadays the main treatment for corneal endotelial dysfunctions. However, there is a worldwide shortage of donor corneas available for transplantation and about 53% of the world's population have no access to corneal transplantation. Generating a complete cornea by tissue engineering is still a tough goal, but an endothelial lamellar graft might be an easier task. In this study, we developed a tissue engineered corneal endothelium by culturing human corneal endothelial cells on a human purified type I collagen membrane...
2016: PloS One
https://www.readbyqxmd.com/read/27906128/two-subunits-of-human-orc-are-dispensable-for-dna-replication-and-proliferation
#6
Etsuko Shibata, Manjari Kiran, Yoshiyuki Shibata, Samarendra Singh, Shashi Kiran, Anindya Dutta
The six-subunit Origin Recognition Complex (ORC) is believed to be an essential eukaryotic ATPase that binds to origins of replication as a ring-shaped heterohexamer to load MCM2-7 and initiate DNA replication. We have discovered that human cell lines in culture proliferate with intact chromosomal origins of replication after disruption of both alleles of ORC2 or of the ATPase subunit, ORC1. The ORC1 or ORC2-depleted cells replicate with decreased chromatin loading of MCM2-7 and become critically dependent on another ATPase, CDC6, for survival and DNA replication...
December 1, 2016: ELife
https://www.readbyqxmd.com/read/27904922/impacts-of-sediment-organic-matter-content-and-ph-on-ecotoxicity-of-coexposure-of-tio2-nanoparticles-and-cadmium-to-freshwater-snails-bellamya-aeruginosa
#7
Taowu Ma, Meng Wang, Shuangjiao Gong, Bin Tian
The environmental factors are expected to affect the ecotoxicity of heavy metals in the presence of engineered nanoparticles (NPs) in aquatic ecosystems. However, in sediment scenario, little is known regarding their impacts on the ecotoxicity of co-exposure of sediment-associated heavy metals and NPs. This study evaluated the impacts of different levels of organic matter (OM) (4.8-11.6%) and pH (6-9) on the ecotoxicological effects of co-exposure of sediment-associated titanium dioxide nanoparticles (TiO2-NPs) and cadmium (Cd) to a freshwater gastropod Bellamya aeruginosa...
November 30, 2016: Archives of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/27904804/mining-snps-in-extracellular-vesicular-transcriptome-of-trypanosoma-cruzi-a-step-closer-to-early-diagnosis-of-neglected-chagas-disease
#8
Pallavi Gaur, Anoop Chaturvedi
One of the newest and strongest members of intercellular communicators, the Extracellular vesicles (EVs) and their enclosed RNAs; Extracellular RNAs (exRNAs) have been acknowledged as putative biomarkers and therapeutic targets for various diseases. Although a very deep insight has not been possible into the physiology of these vesicles, they are believed to be involved in cell-to-cell communication and host-pathogen interactions. EVs might be significantly helpful in discovering biomarkers for possible target identification as well as prognostics, diagnostics and developing vaccines...
2016: PeerJ
https://www.readbyqxmd.com/read/27903966/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-through-inhibition-of-multiple-chaperone-proteins-and-via-the-actions-of-cyclic-gmp-and-nitric-oxide
#9
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Sarah Gordon, Paul Dent
Phosphodiesterase 5 (PDE5) inhibitors prevent the breakdown of cGMP that results in prolonged protein kinase G activation and the generation of nitric oxide. PDE5 inhibitors enhanced the anti-NSCLC cell effects of the NSCLC therapeutic pemetrexed. [Pemetrexed + sildenafil] activated an eIF2α - ATF4 - CHOP - Beclin1 pathway causing formation of toxic autophagosomes; activated a protective IRE1 - XBP-1 - chaperone induction pathway; and activated a toxic eIF2α - CHOP - DR4 / DR5 / CD95 induction pathway. [Pemetrexed + sildenafil] reduced the expression of c-FLIP-s, MCL-1 and BCL-XL that was blocked in a cell-type -dependent fashion by either over-expression of HSP90 / GRP78 / HSP70 / HSP27 or by blockade of eIF2α-CHOP signaling...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903584/src-independent-erk-signaling-through-the-%C3%AE-3-isoform-of-na-k-atpase
#10
Namrata Madan, Yunhui Xu, Qiming Duan, Moumita Banerjee, Isabel Larre, Sandrine V Pierre, Zijian Xie
The Na/K-ATPase α1 polypeptide supports both ion pumping and signaling functions. The Na/K-ATPase α3 polypeptide differs from α1 in both its primary structure and its tissue distribution. Alpha3 expression seems particularly important in neurons, and recent clinical evidence supports a unique role of this isoform in normal brain function. The nature of this specific role of α3 has remained elusive, because the ubiquitous presence of α1 has hindered efforts to characterize α3-specific functions in mammalian cell systems...
November 30, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27901474/cerebellar-neurochemical-and-histopathological-changes-in-rat-model-of-parkinson-s-disease-induced-by-intrastriatal-injection-of-rotenone
#11
Yasser A Khadrawy, Iman M Mourad, Haitham S Mohammed, Neveen A Noor, Heba S Aboul Ezz
The aim of the present work was to investigate the neurochemical changes induced in the cerebellum of rat model of Parkinson's disease (PD). Rats were divided into two groups; control and rat model of PD induced by the intrastriatal injection of rotenone. As compared to control, a significant increase in the excitatory amino acid neurotransmitters; glutamate and aspartate together with a significant decrease in the inhibitory amino acids, GABA, glycine and taurine were observed in the cerebellum of rat model of PD...
November 30, 2016: General Physiology and Biophysics
https://www.readbyqxmd.com/read/27901467/structural-basis-for-the-disaggregase-activity-and-regulation-of-hsp104
#12
Alexander Heuck, Sonja Schitter-Sollner, Marcin Józef Suskiewicz, Robert Kurzbauer, Juliane Kley, Alexander Schleiffer, Pascaline Rombaut, Franz Herzog, Tim Clausen
The Hsp104 disaggregase is a two-ring ATPase machine that rescues various forms of non-native proteins including the highly resistant amyloid fibers. The structural-mechanistic underpinnings of how the recovery of toxic protein aggregates is promoted and how this potent unfolding activity is prevented from doing collateral damage to cellular proteins are not well understood. Here, we present structural and biochemical data revealing the organization of Hsp104 from Chaetomium thermophilum at 3.7 Å resolution...
November 30, 2016: ELife
https://www.readbyqxmd.com/read/27899793/bacterial-proteases-untapped-antimicrobial-drug-targets
#13
REVIEW
Elizabeth Culp, Gerard D Wright
Bacterial proteases are an extensive collection of enzymes that have vital roles in cell viability, stress response and pathogenicity. Although their perturbation clearly offers the potential for antimicrobial drug development, both as traditional antibiotics and anti-virulence drugs, they are not yet the target of any clinically used therapeutics. Here we describe the potential for and recent progress in the development of compounds targeting bacterial proteases with a focus on AAA+ family proteolytic complexes and signal peptidases (SPs)...
November 30, 2016: Journal of Antibiotics
https://www.readbyqxmd.com/read/27899691/high-throughput-spectral-and-lifetime-based-fret-screening-in-living-cells-to-identify-small-molecule-effectors-of-serca
#14
Tory M Schaaf, Kurt C Peterson, Benjamin D Grant, Prachi Bawaskar, Samantha Yuen, Ji Li, Joseph M Muretta, Gregory D Gillispie, David D Thomas
A robust high-throughput screening (HTS) strategy has been developed to discover small-molecule effectors targeting the sarco/endoplasmic reticulum calcium ATPase (SERCA), based on a fluorescence microplate reader that records both the nanosecond decay waveform (lifetime mode) and the complete emission spectrum (spectral mode), with high precision and speed. This spectral unmixing plate reader (SUPR) was used to screen libraries of small molecules with a fluorescence resonance energy transfer (FRET) biosensor expressed in living cells...
November 29, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27899634/homologous-recombination-mediated-by-the-mycobacterial-adnab-helicase-without-end-resection-by-the-adnab-nucleases
#15
Richa Gupta, Mihaela-Carmen Unciuleac, Stewart Shuman, Michael S Glickman
Current models of bacterial homologous recombination (HR) posit that extensive resection of a DNA double-strand break (DSB) by a multisubunit helicase-nuclease machine (e.g. RecBCD, AddAB or AdnAB) generates the requisite 3' single-strand DNA substrate for RecA-mediated strand invasion. AdnAB, the helicase-nuclease implicated in mycobacterial HR, consists of two subunits, AdnA and AdnB, each composed of an N-terminal ATPase domain and a C-terminal nuclease domain. DSB unwinding by AdnAB in vitro is stringently dependent on the ATPase activity of the 'lead' AdnB motor translocating on the 3' ssDNA strand, but not on the putative 'lagging' AdnA ATPase...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899503/postreplication-roles-of-the-brucella-virb-type-iv-secretion-system-uncovered-via-conditional-expression-of-the-virb11-atpase
#16
Erin P Smith, Cheryl N Miller, Robert Child, Jennifer A Cundiff, Jean Celli
: Brucella abortus, the bacterial agent of the worldwide zoonosis brucellosis, primarily infects host phagocytes, where it undergoes an intracellular cycle within a dedicated membrane-bound vacuole, the Brucella-containing vacuole (BCV). Initially of endosomal origin (eBCV), BCVs are remodeled into replication-permissive organelles (rBCV) derived from the host endoplasmic reticulum, a process that requires modulation of host secretory functions via delivery of effector proteins by the Brucella VirB type IV secretion system (T4SS)...
November 29, 2016: MBio
https://www.readbyqxmd.com/read/27899501/unraveling-fungal-radiation-resistance-regulatory-networks-through-the-genome-wide-transcriptome-and-genetic-analyses-of-cryptococcus-neoformans
#17
Kwang-Woo Jung, Dong-Hoon Yang, Min-Kyu Kim, Ho Seong Seo, Sangyong Lim, Yong-Sun Bahn
The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. We found that genes involved in DNA damage repair systems were upregulated in response to gamma radiation...
November 29, 2016: MBio
https://www.readbyqxmd.com/read/27896900/molecular-features-of-copper-binding-proteins-involved-in-copper-homeostasis
#18
REVIEW
Giuseppe Inesi
Copper has a wide and important role in biological systems, determining conformation and activity of many metalloproteins and enzymes, such as cytochrome oxidase and superoxide dismutase . Furthermore, due to its possible reactivity with nonspecific proteins and toxic effects, elaborate systems of absorption, concentration buffering, delivery to specific protein sites and elimination, require a complex system including small carriers, chaperones and active transporters. The P-type copper ATPases ATP7A and ATP7B provide an important system for acquisition, active transport, distribution and elimination of copper...
November 28, 2016: IUBMB Life
https://www.readbyqxmd.com/read/27896136/attention-deficit-hyperactivity-disorder-suffers-from-mitochondrial-dysfunction
#19
Poonam Verma, Alpana Singh, Dominic Ngima Nthenge-Ngumbau, Usha Rajamma, Swagata Sinha, Kanchan Mukhopadhyay, Kochupurackal P Mohanakumar
BACKGROUND: Pathophysiology of attention-deficit hyperactivity disorder (ADHD) is not known, and therefore the present study investigated mitochondrial defects, if any in cybrids created from patients and control population. METHODS: To investigate mitochondrial pathology in ADHD, cybrids cell lines were created from ADHD probands and controls by fusing their platelets with ρ(0)-cells prepared from SH-SY5Y neuroblastoma cell line. Cellular respiration, oxidative stress, mitochondrial membrane potential and morphology were evaluated employing oxygraph, mitochondria-specific fluorescence staining and evaluation by FACS, and immunocytochemistry...
December 2016: BBA Clinical
https://www.readbyqxmd.com/read/27895739/gene-expression-profiling-of-the-8q22-24-position-in-human-breast-cancer-tspyl5-mtdh-atad2-and-ccne2-genes-are-implicated-in-oncogenesis-while-wisp1-and-ext1-genes-may-predict-a-risk-of-metastasis
#20
Afsoon Taghavi, Mohammad Esmaeil Akbari, Mohammad Hashemi-Bahremani, Nahid Nafissi, Ahad Khalilnezhad, Seyed Mohammad Poorhosseini, Feyzollah Hashemi-Gorji, Vahid Reza Yassaee
Gene expression profiling has been suggested to predict breast cancer outcome. The prognostic value of the 8q22-24 position in breast cancer remains to be elucidated. The present study evaluated expression patterns of the genes located at this position in metastatic and non-metastatic breast cancer. A total of 85 patients with recurrent/metastatic (n=15) and non-metastatic (n=70) early-stage, estrogen receptor-positive and lymph node-negative breast tumors were included. In addition, 15 normal breast tissue samples were used as controls...
November 2016: Oncology Letters
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