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https://www.readbyqxmd.com/read/28930842/type-4b-hereditary-hemochromatosis-associated-with-a-novel-mutation-in-the-slc40a1-gene-a-case-report-and-a-review-of-the-literature
#1
Wei Zhang, Tingxia Lv, Jian Huang, Xiaojuan Ou
RATIONALE: Hereditary hemochromatosis can be divided into HFE- and non-HFE-related based on genetic mutations in different genes. HFE-related hemochromatosis is the most common inherited genetic disease in European populations but rare in Asia-pacific region. Recently, non-HFE-related hemochromatosis has been reported in patients from the Asian countries. PATIENT CONCERNS: We report the case of a 48-year-old Chinese Han woman who presented with abnormal liver function, diabetes mellitus, hyperferritinemia, and high transferrin saturation, with severe iron overload in parenchymal cells, Kupffer cells, and periportal fibrosis on liver biopsy...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28928454/a-comprehensive-characterization-of-pnca-polymorphisms-that-confer-resistance-to-pyrazinamide
#2
Adam N Yadon, Kashmeel Maharaj, John H Adamson, Yi-Pin Lai, James C Sacchettini, Thomas R Ioerger, Eric J Rubin, Alexander S Pym
Tuberculosis chemotherapy is dependent on the use of the antibiotic pyrazinamide, which is being threatened by emerging drug resistance. Resistance is mediated through mutations in the bacterial gene pncA. Methods for testing pyrazinamide susceptibility are difficult and rarely performed, and this means that the full spectrum of pncA alleles that confer clinical resistance to pyrazinamide is unknown. Here, we performed in vitro saturating mutagenesis of pncA to generate a comprehensive library of PncA polymorphisms resultant from a single-nucleotide polymorphism...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28927677/std-nmr-experiments-identify-a-structural-motif-with-novel-second-site-activity-against-west-nile-virus-ns2b-ns3-protease
#3
Tobias Schöne, Lena Lisbeth Grimm, Naoki Sakai, Linlin Zhang, Rolf Hilgenfeld, Thomas Peters
West Nile virus (WNV) belongs to the genus Flavivirus of the family Flaviviridae. This mosquito-borne virus that is highly pathogenic to humans has been evolving into a global threat during the past two decades. Despite many efforts, neither antiviral drugs nor vaccines are available. The viral protease NS2B-NS3(pro) is essential for viral replication, and therefore it is considered a prime drug target. However, success in the development of specific NS2B-NS3(pro) inhibitors had been moderate so far. In the search for new structural motifs with binding affinity for NS2B-NS3(pro), we have screened a fragment library, the Maybridge Ro5 library, employing saturation transfer difference (STD) NMR experiments as readout...
September 16, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28920118/hybrid-magnetic-iron-oxide-nanoparticles-with-tunable-field-directed-self-assembly
#4
Vikash Malik, Antara Pal, Olivier Pravaz, Jérôme J Crassous, Simon Granville, Bernard Grobety, Ann M Hirt, Hervé Dietsch, Peter Schurtenberger
We describe the synthesis of hybrid magnetic ellipsoidal nanoparticles that consist of a mixture of two different iron oxide phases, hematite (α-Fe2O3) and maghemite (γ-Fe2O3), and characterize their magnetic field-driven self-assembly. We demonstrate that the relative amount of the two phases can be adjusted in a continuous way by varying the reaction time during the synthesis, leading to strongly varying magnetic properties of the particles. Not only does the saturation magnetization increase dramatically as the composition of the spindles changes from hematite to maghemite, but also the direction of the induced magnetic moment changes from being parallel to the short axis of the spindle to being perpendicular to it...
September 18, 2017: Nanoscale
https://www.readbyqxmd.com/read/28919244/does-synaesthesia-age-changes-in-the-quality-and-consistency-of-synaesthetic-associations
#5
Julia Simner, Alberta Ipser, Rebecca Smees, James Alvarez
Developmental grapheme-colour synaesthesia is a rare condition in which colours become automatically paired with letters or digits in the minds of certain individuals during childhood, and remain paired into adulthood. Although synaesthesia is well understood in younger adults almost nothing is known about synaesthesia in aging. We present the first evidence that aging desaturates synaesthetic colours in the minds of older synaesthetes, and we show for the first time that aging affects the key diagnostic measure of synaesthesia (consistency of colours over time)...
September 14, 2017: Neuropsychologia
https://www.readbyqxmd.com/read/28906493/rapid-curation-of-gene-disruption-collections-using-knockout-sudoku
#6
Isao A Anzai, Lev Shaket, Oluwakemi Adesina, Michael Baym, Buz Barstow
Knockout Sudoku is a method for the construction of whole-genome knockout collections for a wide range of microorganisms with as little as 3 weeks of dedicated labor and at a cost of ∼$10,000 for a collection for a single organism. The method uses manual 4D combinatorial pooling, next-generation sequencing, and a Bayesian inference algorithm to rapidly process and then accurately annotate the extremely large progenitor transposon insertion mutant collections needed to achieve saturating coverage of complex microbial genomes...
October 2017: Nature Protocols
https://www.readbyqxmd.com/read/28900609/genes-contributing-to-porphyromonas-gingivalis-fitness-in-abscess-and-epithelial-cell-colonization-environments
#7
Daniel P Miller, Justin A Hutcherson, Yan Wang, Zuzanna M Nowakowska, Jan Potempa, Deborah R Yoder-Himes, David A Scott, Marvin Whiteley, Richard J Lamont
Porphyromonas gingivalis is an important cause of serious periodontal diseases, and is emerging as a pathogen in several systemic conditions including some forms of cancer. Initial colonization by P. gingivalis involves interaction with gingival epithelial cells, and the organism can also access host tissues and spread haematogenously. To better understand the mechanisms underlying these properties, we utilized a highly saturated transposon insertion library of P. gingivalis, and assessed the fitness of mutants during epithelial cell colonization and survival in a murine abscess model by high-throughput sequencing (Tn-Seq)...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28900255/saturated-mutagenesis-of-ketoisovalerate-decarboxylase-v461-enabled-specific-synthesis-of-1-pentanol-via-the-ketoacid-elongation-cycle
#8
Grey S Chen, Siang Wun Siao, Claire R Shen
Iterative ketoacid elongation has been an essential tool in engineering artificial metabolism, in particular the synthetic alcohols. However, precise control of product specificity is still greatly challenged by the substrate promiscuity of the ketoacid decarboxylase, which unselectively hijacks ketoacid intermediates from the elongation cycle along with the target ketoacid. In this work, preferential tuning of the Lactococcus lactis ketoisovalerate decarboxylase (Kivd) specificity toward 1-pentanol synthesis was achieved via saturated mutagenesis of the key residue V461 followed by screening of the resulting alcohol spectrum...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899523/validation-of-the-screening-tool-apnealink-%C3%A2-in-comparison-to%C3%A2-polysomnography-for-the-diagnosis-of-sleep-disordered-breathing%C3%A2-in-children-and-adolescents
#9
Florian Stehling, Judith Keull, Margarete Olivier, Jörg Große-Onnebrink, Uwe Mellies, Boris A Stuck
OBJECTIVE: While out-of-center testing was introduced as an alternative for the diagnosis of obstructive sleep apnea in adults, polysomnography (PSG) is still considered mandatory in the diagnosis of sleep-disordered breathing (SDB) in children. The purpose of this study was to validate the outpatient screening device ApneaLink(®) in comparison to PSG in children and adolescents for the diagnosis of SDB. METHODS: Sixty consecutive children and adolescents (10.4 ± 6...
September 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28893793/chemical-genomic-interaction-profiling-reveals-determinants-of-intrinsic-antibiotic-resistance-in-mycobacterium-tuberculosis
#10
Weizhen Xu, Michael A DeJesus, Nadine Rücker, Curtis A Engelhart, Meredith G Wright, Claire Healy, Kan Lin, Ruojun Wang, Sae Woong Park, Thomas R Ioerger, Dirk Schnappinger, Sabine Ehrt
Chemotherapy for tuberculosis (TB) is lengthy and could benefit from synergistic adjuvant therapeutics that enhance current and novel drug regimens. To identify genetic determinants of intrinsic antibiotic susceptibility in Mycobacterium tuberculosis (Mtb) we applied a chemical genetic interaction (CGI) profiling approach. We screened a saturated transposon mutant library and identified mutants that exhibit altered fitness in the presence of partially-inhibitory concentrations of rifampicin, ethambutol, isoniazid, vancomycin and meropenem, antibiotics of diverse mechanisms-of-action...
September 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28886937/studies-of-drug-interactions-with-alpha1-acid-glycoprotein-by-using-on-line-immunoextraction-and-high-performance-affinity-chromatography
#11
Cong Bi, Ryan Matsuda, Chenhua Zhang, Zitha Isingizwe, William Clarke, David S Hage
A method that combined on-line immunoextraction with high-performance affinity chromatography was developed to examine the binding of drugs with α1-acid glycoprotein (AGP). Affinity microcolumns containing immobilized polyclonal anti-AGP antibodies were developed that had a capture efficiency of up to 98.4% for AGP and a binding capacity of 0.72nmol AGP when using a 20mm×2.1mm i.d. microcolumn. These microcolumns were employed in various formats to examine the binding of drugs to normal AGP and AGP that had been adsorbed from serum samples for patients with systemic lupus erythematosus (SLE)...
August 31, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28885215/hyperspectral-imaging-as-a-novel-diagnostic-tool-in-microcirculation-of-wounds
#12
Georg Daeschlein, Inga Langner, Thomas Wild, Sebastian von Podewils, Claudia Sicher, Thomas Kiefer, Michael Jünger
Monitoring of perfusion is a cornerstone in surgery, phlebology and basic science to proof wound healing by interventions. In chronic wound management it is of utmost importance to realize and parametrize wound bed perfusion to verify actual, and plan further treatment by noninvasive diagnostics. Up to now monitoring is based on visual inspection of wounds as conventionally practiced over more than decades. The main problems of visual inspection are the lack of standardization and comparability because of interindividual variations...
September 4, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/28881100/an-engineered-glycerol-dehydratase-with-improved-activity-for-the-conversion-of-meso-2-3-butanediol-to-butanone
#13
Danielle J Maddock, Monica L Gerth, Wayne M Patrick
There is substantial interest in engineering microorganisms to produce industrial chemicals that are currently derived from petroleum. One of these petrochemicals is butanone, which could be produced from microbially synthesized 2,3-butanediol through the action of a suitable dehydratase enzyme. Unfortunately, however, there are no known enzymes that natively catalyze this reaction. In this work, we set out to engineer the B12 -dependent glycerol dehydratase from Klebsiella pneumoniae (KpGDHt), in order to increase its activity for the conversion of meso-2,3-butanediol into butanone...
September 7, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28872709/implementing-higher-oxygen-saturation-targets-reduced-the-impact-of-poor-weight-gain-as-a-predictor-for-retinopathy-of-prematurity
#14
Pia Lundgren, Anna-Lena Hård, Åsa Wilde, Chatarina Löfqvist, Lois E H Smith, Ann Hellström
AIM: This study evaluated poor weight gain as a risk factor for infants who required treatment for retinopathy of prematurity (ROP), by comparing those born before and after the implementation of higher oxygen saturation (SpO2 ) targets at the Queen Silvia Children's Hospital, Gothenburg, Sweden. METHODS: We compared infants born at less than 31 weeks, who were screened and, or, treated for ROP: 127 in 2011-2012 when SpO2 targets were 88-92% and 142 in 2015-2016 when they were 91-95%...
September 5, 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/28865431/uncommon-presentation-of-a-rare-tumour-incidental-finding-in-an-asymptomatic-patient-case-report-and-comprehensive-review-of-the-literature-on-intrapericardial-solitary-fibrous-tumours
#15
Csilla Czimbalmos, Ibolya Csecs, Miklos Polos, Elektra Bartha, Nikolette Szucs, Attila Toth, Pal Maurovich-Horvat, David Becker, Zoltan Sapi, Zoltan Szabolcs, Bela Merkely, Hajnalka Vago
BACKGROUND: A solitary fibrous tumour is a rare, mainly benign spindle cell mesenchymal tumour most commonly originating from the pleura. An intrapericardial location of a solitary fibrous tumour is extremely unusual. We present a case of an asymptomatic patient with a slow-growing massive benign cardiac solitary fibrous tumour. CASE PRESENTATION: A 37-year-old asymptomatic female patient was referred to our hospital with an enlarged cardiac silhouette found on her screening chest X-ray...
September 2, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28863145/associations-between-endothelial-dysfunction-and-clinical-and-laboratory-parameters-in-children-and-adolescents-with-sickle-cell-anemia
#16
Rozana Santos Teixeira, Regina Terse-Ramos, Tatiane Anunciação Ferreira, Vinícius Ramos Machado, Marya Izadora Perdiz, Isa Menezes Lyra, Valma Lopes Nascimento, Ney Boa-Sorte, Bruno B Andrade, Ana Marice Ladeia
BACKGROUND: Hematological changes can drive damage of endothelial cells, which potentially lead to an early endothelial dysfunction in patients with sickle cell anemia (SCA). An association may exist between endothelial dysfunction and several clinical manifestations of SCA. The present study aims to evaluate the links between changes in endothelial function and clinical and laboratory parameters in children and adolescents with SCA. METHODS: This study included 40 children and adolescents with stable SCA as well as 25 healthy children; aged 6-18 years...
2017: PloS One
https://www.readbyqxmd.com/read/28862838/locally-resolved-electron-emission-area-and-unified-view-of-field-emission-from-ultrananocrystalline-diamond-films
#17
Oksana Chubenko, Stanislav Baturin, Kiran K Kovi, Anirudha Sumant, Sergey V Baryshev
In this paper we study the effect of the actual, locally resolved, field emission area on electron emission characteristics of uniform planar conductive nitrogen-incorporated ultrananocrystalline diamond ((N)UNCD) field emitters. High resolution imaging experiments were carried out in a field emission microscope with a specialty anode imaging screen, such that electron emission micrographs were taken concurrently with measurements of I-V characteristics. A novel automated image processing algorithm was applied to process the extensive imaging datasets and calculate the emission area per image...
September 1, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28851572/zebrafish-as-an-early-stage-screening-tool-to-study-the-systemic-circulation-of-nanoparticulate-drug-delivery-systems-in-vivo
#18
Sandro Sieber, Philip Grossen, Pascal Detampel, Salome Siegfried, Dominik Witzigmann, Jörg Huwyler
Nanomedicines have gained much attention for the delivery of small molecules or nucleic acids as treatment options for many diseases. However, the transfer from experimental systems to in vivo applications remains a challenge since it is difficult to assess their circulation behavior in the body at an early stage of drug discovery. Thus, innovative and improved concepts are urgently needed to overcome this issue and to close the gap between empiric nanoparticle design, in vitro assessment, and first in vivo experiments using rodent animal models...
August 26, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28839307/pulse-oximetry-as-a-screening-tool-for-critical-congenital-heart-defects-in-newborns
#19
Muhammad Shahzad, Talal Waqar, Khawaja Ahmad Irfan Waheed, Rafia Gul, Syeda Tahseen Fatima
OBJECTIVE: To evaluate the effectiveness of pulse oximetry as a screening tool for critical congenital heart defects in newborns. METHODS: This cross-sectional study was conducted at the neonatology department of the Children's Hospital and the Institute of Child Health, Lahore, Pakistan, from January to June 2016, and comprised neonates aged up to 07 days. Babies with a prenatal diagnosis of heart defects and those whose parents refused to give consent were excluded...
August 2017: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/28832623/variants-of-sequence-family-b-thermococcus-kodakaraensis-dna-polymerase-with-increased-mismatch-extension-selectivity
#20
Claudia Huber, Andreas Marx
Fidelity and selectivity of DNA polymerases are critical determinants for the biology of life, as well as important tools for biotechnological applications. DNA polymerases catalyze the formation of DNA strands by adding deoxynucleotides to a primer, which is complementarily bound to a template. To ensure the integrity of the genome, DNA polymerases select the correct nucleotide and further extend the nascent DNA strand. Thus, DNA polymerase fidelity is pivotal for ensuring that cells can replicate their genome with minimal error...
2017: PloS One
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