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https://www.readbyqxmd.com/read/28820969/a-disulfide-stabilized-human-vl-single-domain-antibody-library-is-a-source-of-soluble-and-highly-thermostable-binders
#1
Kevin A Henry, Hiba Kandalaft, Michael J Lowden, Martin A Rossotti, Henk van Faassen, Greg Hussack, Yves Durocher, Dae Young Kim, Jamshid Tanha
We have previously shown that incorporation of a second intradomain disulfide linkage into camelid VHH and human VH/VL single-domain antibodies confers increased thermostability. Here, we explored the effects of introducing an additional disulfide linkage, formed between Cys48 and Cys64 (Kabat numbering), into a phage-displayed synthetic human VL library. In comparison to an identical library bearing only the highly conserved Cys23-Cys88 disulfide linkage, the disulfide-stabilized VL library tolerated a similar degree of randomization but retained a higher level of functional diversity after selection with protein L...
August 15, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28820968/reduced-activin-receptor-like-kinase-1-activity-promotes-cardiac-fibrosis-in-heart-failure
#2
Kevin J Morine, Xiaoying Qiao, Vikram Paruchuri, Mark J Aronovitz, Emily E Mackey, Lyanne Buiten, Jonathan Levine, Keshan Ughreja, Prerna Nepali, Robert M Blanton, S Paul Oh, Richard H Karas, Navin K Kapur
INTRODUCTION: Activin receptor-like kinase 1 (ALK1) mediates signaling via the transforming growth factor beta-1 (TGFβ1), a pro-fibrogenic cytokine. No studies have defined a role for ALK1 in heart failure. HYPOTHESIS: We tested the hypothesis that reduced ALK1 expression promotes maladaptive cardiac remodeling in heart failure. METHODS AND RESULTS: In patients with advanced heart failure referred for left ventricular (LV) assist device implantation, LV Alk1 mRNA and protein levels were lower than control LV obtained from patients without heart failure...
July 18, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28820910/impaired-dendritic-growth-and-positioning-of-cortical-pyramidal-neurons-by-activation-of-aryl-hydrocarbon-receptor-signaling-in-the-developing-mouse
#3
Eiki Kimura, Ken-Ichiro Kubo, Toshihiro Endo, Wenting Ling, Kazunori Nakajima, Masaki Kakeyama, Chiharu Tohyama
The basic helix-loop-helix (bHLH) transcription factors exert multiple functions in mammalian cerebral cortex development. The aryl hydrocarbon receptor (AhR), a member of the bHLH-Per-Arnt-Sim subfamily, is a ligand-activated transcription factor reported to regulate nervous system development in both invertebrates and vertebrates, but the functions that AhR signaling pathway may have for mammalian cerebral cortex development remains elusive. Although the endogenous ligand involved in brain developmental process has not been identified, the environmental pollutant dioxin potently binds AhR and induces abnormalities in higher brain function of laboratory animals...
2017: PloS One
https://www.readbyqxmd.com/read/28820889/altered-fetal-growth-placental-abnormalities-and-stillbirth
#4
Radek Bukowski, Nellie I Hansen, Halit Pinar, Marian Willinger, Uma M Reddy, Corette B Parker, Robert M Silver, Donald J Dudley, Barbara J Stoll, George R Saade, Matthew A Koch, Carol Hogue, Michael W Varner, Deborah L Conway, Donald Coustan, Robert L Goldenberg
BACKGROUND: Worldwide, stillbirth is one of the leading causes of death. Altered fetal growth and placental abnormalities are the strongest and most prevalent known risk factors for stillbirth. The aim of this study was to identify patterns of association between placental abnormalities, fetal growth, and stillbirth. METHODS AND FINDINGS: Population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in 5 geographic areas in the U...
2017: PloS One
https://www.readbyqxmd.com/read/28820427/a-review-of-the-neuropsychological-dimensions-of-tourette-syndrome
#5
REVIEW
Simon Morand-Beaulieu, Julie B Leclerc, Philippe Valois, Marc E Lavoie, Kieron P O'Connor, Bruno Gauthier
Neurocognitive functioning in Tourette syndrome (TS) has been the subject of intensive research in the past 30 years. A variety of impairments, presumably related to frontal and frontostriatal dysfunctions, have been observed. These impairments were found in various domains, such as attention, memory, executive functions, language, motor and visuomotor functions, among others. In line with contemporary research, other neurocognitive domains have recently been explored in TS, bringing evidence of altered social reasoning, for instance...
August 18, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28820396/the-role-of-mtor-inhibitors-and-hmg-coa-reductase-inhibitors-on-young-and-old-endothelial-cell-functions-critical-for-re-endothelialisation-after-percutaneous-coronary-intervention-an-in-vitro-study
#6
K Korybalska, E Kawka, A Breborowicz, J Witowski
Percutaneous coronary intervention (PCI) has become a standard treatment in patients with acute coronary syndrome. However, it is associated with endothelial cell denudation, which may predispose to in-stent thrombosis and restenosis. Pharmacological methods which prevent restenosis can delay post-PCI re-endothelialisation. We have therefore examined how atorvastatin (HMG-CoA reductase inhibitor), sirolimus and everolimus (mTOR inhibitors) affect young and old endothelial cell functions which are responsible for wound healing after PCI...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28820294/k-deficiency-caused-defects-in-renal-tubular-cell-proliferation-oxidative-stress-response-tissue-repair-and-tight-junction-integrity-but-enhanced-energy-production-proteasome-function-and-cellular-k-uptake
#7
Chompunoot Kapincharanon, Visith Thongboonkerd
Hypokalemia is a common electrolyte disorder in hospitalized patients and those with chronic diseases and is associated with renal tubular injury. Our recent expression proteomics study revealed changes in levels of several proteins in renal tubular cells during K(+) deficiency. However, functional significance and mechanisms underlying such changes remained unclear. The present study, thus, aimed to investigate functional changes of renal tubular cells induced by K(+) deficiency. MDCK cells were maintained in normal-K(+) (ANK; [K(+)] = 5...
August 18, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28820073/immunomodulatory-role-of-arsenic-on-regulatory-t-cells
#8
Rizwanul Haque, Archana Chaudhary, Nadra Sadaf
Background and objective-Chronic Arsenic (As) exposure continued to be a cause of major problem associated with different kind of diseases including skin problem and different types of cancer. As exposure leads to numerous other pathological conditions that affect millions of people worldwide on a regular basis. It was recently established that As toxicity affects immune system and modulate the function and survival of cells involved in immune regulation. Arsenic trioxide (As2O3) was reported to be an effective apoptosis inducer in a variety of cell types...
August 17, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28819687/central-not-peripheral-vestibular-processing-impairs-gait-coordination
#9
Yoav Gimmon, Jennifer Millar, Rebecca Pak, Elizabeth Liu, Michael C Schubert
Gait coordination is generated by neuronal inter-connections between central pattern generators in the spinal cord governed by cortical areas. Malfunction of central vestibular processing areas generates vestibular symptoms in the absence of an identifiable peripheral vestibular system lesion. Walking in the dark enforces a coordinated afference primarily from the vestibular and somatosensory systems. We hypothesized that patients with aberrant central vestibular processing would demonstrate unique gait characteristics, and have impaired gait coordination compared with those patients with abnormal peripheral vestibular function and healthy controls...
August 17, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28819681/low-level-environmental-cadmium-exposure-induces-kidney-tubule-damage-in-the-general-population-of-korean-adults
#10
Sang-Yong Eom, Mi-Na Seo, Young-Sub Lee, Kyung-Su Park, Young-Seoub Hong, Seok-Joon Sohn, Yong-Dae Kim, Byung-Sun Choi, Ji-Ae Lim, Ho-Jang Kwon, Heon Kim, Jung-Duck Park
Cadmium (Cd) is the most potent nephrotoxic heavy metal and may affect bone; it also has a long biological half-life in the human body. This study was designed to assess the effect of environmental low-level Cd exposure on kidney function and bone in the general population. The subjects of this cross-sectional study were 1907 healthy Korean adults who had not been exposed to Cd occupationally. We analyzed the concentrations of Cd in the urine, markers of renal tubule damage, such as β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) activity in the urine, calculated the estimated glomerular filtration rate (eGFR) using serum creatinine, and measured bone mineral density (BMD)...
August 17, 2017: Archives of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/28819220/nosema-ceranae-fipronil-and-their-combination-compromise-honey-bee-reproduction-via-changes-in-male-physiology
#11
Guillaume Kairo, David G Biron, Faten Ben Abdelkader, Marc Bonnet, Sylvie Tchamitchian, Marianne Cousin, Claudia Dussaubat, Boris Benoit, André Kretzschmar, Luc P Belzunces, Jean-Luc Brunet
The honey bee is threatened by biological agents and pesticides that can act in combination to induce synergistic effects on its physiology and lifespan. The synergistic effects of a parasite/pesticide combination have been demonstrated on workers and queens, but no studies have been performed on drones despite their essential contribution to colony sustainability by providing semen diversity and quality. The effects of the Nosema ceranae/fipronil combination on the life traits and physiology of mature drones were examined following exposure under semi-field conditions...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819185/deletion-of-ep4-in-s100a4-lineage-cells-reduces-scar-tissue-formation-during-early-but-not-later-stages-of-tendon-healing
#12
Jessica E Ackerman, Katherine T Best, Regis J O'Keefe, Alayna E Loiselle
Tendon injuries heal via scar tissue rather than regeneration. This healing response forms adhesions between the flexor tendons in the hand and surrounding tissues, resulting in impaired range of motion and hand function. Mechanistically, inflammation has been strongly linked to adhesion formation, and Prostaglandin E2 (PGE2) is associated with both adhesion formation and tendinopathy. In the present study we tested the hypothesis that deletion of the PGE2 receptor EP4 in S100a4-lineage cells would decrease adhesion formation...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819097/the-non-coding-rna-bc1-regulates-experience-dependent-structural-plasticity-and-learning
#13
Victor Briz, Leonardo Restivo, Emanuela Pasciuto, Konrad Juczewski, Valentina Mercaldo, Adrian C Lo, Pieter Baatsen, Natalia V Gounko, Antonella Borreca, Tiziana Girardi, Rossella Luca, Julie Nys, Rogier B Poorthuis, Huibert D Mansvelder, Gilberto Fisone, Martine Ammassari-Teule, Lutgarde Arckens, Patrik Krieger, Rhiannon Meredith, Claudia Bagni
The brain cytoplasmic (BC1) RNA is a non-coding RNA (ncRNA) involved in neuronal translational control. Absence of BC1 is associated with altered glutamatergic transmission and maladaptive behavior. Here, we show that pyramidal neurons in the barrel cortex of BC1 knock out (KO) mice display larger excitatory postsynaptic currents and increased spontaneous activity in vivo. Furthermore, BC1 KO mice have enlarged spine heads and postsynaptic densities and increased synaptic levels of glutamate receptors and PSD-95...
August 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28819094/atrioventricular-conduction-delay-predicts-impaired-exercise-capacity-in-patients-with-heart-failure-with-reduced-ejection-fraction
#14
Jakub Stępniewski, Grzegorz Kopeć, Wojciech Magoń, Piotr Podolec
BACKGROUND Atrioventricular conduction delay (AVCD) impairs left ventricular (LV) filling and consequently leads to a reduction of cardiac output. We hypothesized that in patients with severely depressed LV function and coexisting intraventricular conduction disturbances (IVCD), AVCD can affect exercise performance. Therefore, we evaluated the association of AVCD and exercise capacity in patients with heart failure (HFREF) and coexisting IVCD. MATERIAL AND METHODS We included patients with stable, chronic HFREF, LVEF <35%, sinus rhythm, and QRS ≥120 ms...
August 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28819076/-molecularly-targeted-therapy-of-spinocerebellar-ataxia-type-1-by-hmgb1
#15
Kyota Fujita, Hitoshi Okazawa
Spinocerebellar ataxia type 1 (SCA1) is an untreatable neurodegenerative disease. We reported a decrease in HMGB1 levels in the nucleus of cerebellar neurons in mouse SCA 1. The decrease in this DNA architectural protein leads to the impairment of DNA repair and transcription, the two essential nuclear functions, and eventually causes neurodegeneration. We have designed a gene therapy using AAV-HMGB1 and tested it using the mouse model. Based on the results of these proof of concept (POC) studies, we are now preparing GMP-level AAV vector and designing human clinical trials...
August 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28819074/-molecular-pathogenesis-of-polyglutamine-diseases
#16
Yuji Takahashi
Polyglutamine diseases result from gain-of-function mutations. The expanded polyglutamine tracts lead to conformational changes in proteins, resulting in their aggregation. The intermediates including monomers or oligomers, are more toxic than the aggregates to neurons. At the molecular level, protein misfolding, transcriptional dysregulation, deranged calcium homeostasis, impaired cytoskeleton/axonal transport, mitochondrial dysfunction, and RNA toxicity contribute to disease progression. Understanding the underlying pathogenesis facilitates development of therapy for polyglutamine diseases...
August 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28819056/effects-of-sublethal-doses-of-thiacloprid-and-its-formulation-calypso-%C3%A2-on-the-learning-and-memory-performance-of-honey-bees
#17
Léa Tison, Sophie Holtz, Amy Adeoye, Önder Kalkan, Nina S Irmisch, Randolf Menzel
Learning and memory play a central role in behavior and communication of foraging bees. We already showed that chronic uptake of the neonicotinoid thiacloprid affects the behavior of honey bees in the field. Foraging behavior, homing success, navigation performance, and social communication were impaired. Thiacloprid collected at a feeding site at low doses accumulates in foragers over time. Here we applied a laboratory standard procedure, the proboscis extension response (PER) conditioning, in order to assess which processes, acquisition, memory consolidation and/or memory retrieval were compromised after bees were fed either with thiacloprid or the formulation of thiacloprid named Calypso(®) at 3 different sublethal doses...
August 17, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28819047/unusual-case-of-bilateral-hand-weakness
#18
Sayan Datta, Jeremy Cosgrove, Taimour Alam, Helen L Ford
A 35-year-old man presented with myalgia and bilateral hand weakness, 3 days after the onset of lethargy, fevers and rigours. The hand weakness caused functional impairment including difficulty pressing keys on his mobile phone. On examination, there was mild bilateral hand weakness with normal reflexes. His serum creatine kinase was mildly raised at 503 U/L (24-195), viral PCR throat swab was negative and electromyogram showed subtle myopathic changes in the distal forearm muscles. Nerve conduction studies found no evidence of neuropathy...
August 17, 2017: Practical Neurology
https://www.readbyqxmd.com/read/28819044/the-parkinson-s-disease-associated-protein-dj-1-plays-a-positive-nonmitochondrial-role-in-endocytosis-in-dictyostelium-cells
#19
Suwei Chen, Sarah J Annesley, Rasha A F Jasim, Vanessa J Musco, Oana Sanislav, Paul R Fisher
The loss of function of DJ-1 caused by mutations of DJ-1 causes a form of familial Parkinson's Disease (PD). However, the role of DJ-1 in healthy and in PD cells is poorly understood. Even its subcellular localization in mammalian cells is uncertain, both cytosolic and mitochondrial locations having been reported. We show here that DJ-1 is normally located in the cytoplasm in healthy Dictyostelium discoideum cells. With its unique life cycle, straightforward genotype-phenotype relationships, experimental accesibility and genetic tractability, Dictyostelium discoideum offers an attractive model to investigate the roles of PD-associated genes...
August 17, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28818903/draft-genome-sequence-of-staphylococcus-aureus-s681-a-tetracycline-sensitive-livestock-associated-methicillin-resistant-clonal-complex-398-strain
#20
Marc J A Stevens, Roger Stephan, Sophia Johler
We present the draft genome sequence of an atypical tetracycline-susceptible livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) strain. It contains 2,817,340 bp and 2,858 coding sequences, including 6 rRNA operons, 56 tRNAs, and 4 noncoding RNA (ncRNA) genes. The strain harbors a tet(M) gene, but 15 point mutations in amino acids are present that likely impair the functionality of TetM.
August 17, 2017: Genome Announcements
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