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https://www.readbyqxmd.com/read/29223927/biochemical-characterization-of-the-ybpci-miniprotein-the-first-carboxypeptidase-inhibitor-isolated-from-yellow-bell-pepper-capsicum-annuum-l-a-novel-contribution-to-the-knowledge-of-miniproteins-stability
#1
Juliana Cotabarren, Mariana Edith Tellechea, Francesc Xavier Avilés, Julia Lorenzo, Walter David Obregón
The cystine-knot metallocarboxypeptidase inhibitors (MCPIs) are peptides that contribute to control proteolytic activity, involved in storage, growth and maintenance of plants. Lately studies reported several MCPIs with potential use in biomedical applications; as anti-cancer, anti-thrombotic, anti-malaric and anti-angiogenic agents. We report the isolation, purification, chemical stability and biochemical characterization of a novel carboxypeptidase A inhibitor (YBPCI) isolated from Capsicum annuum L. var...
December 6, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/29223310/cystinuria-one-possible-reason-for-kidney-and-salivary-gland-lithiasis-relationship
#2
Marc-Kevin Le Roux, Nicolas Graillon, Jean-Marc Foletti, Cyrille Chossegros
Salivary gland lithiasis affects 1 to 2% of adults. The submandibular glands are concerned in 87% of cases. An association between kidney and salivary lithiases, although often mentioned, has rarely been observed. We relate an exceptional case of parotid and submandibular cystine sialolithiasis with kidney cystine lithiasis in a patient with cystinuria. Cystine lithiasis occurs in 1% of kidney lithiasis cases. The purpose of this article is to discuss the arguments, diagnosis, and therapeutic attitude in front of salivary cystine lithiasis...
November 22, 2017: Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/29222417/insulin-in-motion-the-a6-a11-disulfide-bond-allosterically-modulates-structural-transitions-required-for-insulin-activity
#3
Bianca van Lierop, Shee Chee Ong, Alessia Belgi, Carlie Delaine, Sofianos Andrikopoulos, Naomi L Haworth, John G Menting, Michael C Lawrence, Andrea J Robinson, Briony E Forbes
The structural transitions required for insulin to activate its receptor and initiate regulation of glucose homeostasis are only partly understood. Here, using ring-closing metathesis, we substitute the A6-A11 disulfide bond of insulin with a rigid, non-reducible dicarba linkage, yielding two distinct stereo-isomers (cis and trans). Remarkably, only the cis isomer displays full insulin potency, rapidly lowering blood glucose in mice (even under insulin-resistant conditions). It also posseses reduced mitogenic activity in vitro...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29219315/calculation-of-standard-reduction-potentials-of-amino-acid-radicals-and-the-effects-of-water-and-incorporation-into-peptides
#4
David M Close, Peter Wardman
Guanine (Guo) is generally accepted as the most easily-oxidized DNA base when cells are subjected to ionizing radiation; calculations of the standard reduction potential of the guanyl radical, Eo(Guo•+/Guo) are within ~ 0.1 V of experimental values in aqueous solution extrapolated to standard conditions. While a number of experimental studies have shown some amino acid radicals have redox properties at pH 7 which suggest or confirm a capacity for radical 'repair' by electron transfer from the amino acid to Guo•+ (or its deprotonated conjugate), the redox properties of the radicals of other amino acids, including methionine, lysine and cystine, are less well characterized...
December 8, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/29217475/in-vitro-drug-release-and-in-vivo-safety-of-vitamin-e-and-cysteamine-loaded-contact-lenses
#5
Phillip Dixon, Richard C Fentzke, Arnab Bhattacharya, Aditya Konar, Sarbani Hazra, Anuj Chauhan
Cystinosis is an orphan disease caused by a genetic mutation that leads to deposition of cystine crystals in many organs including cornea. Ophthalmic manifestation of the disease can be treated with hourly instillation of cysteamine eye drops. The hourly eye drop instillation is tedious to the patients leading to poor compliance and additionally, significant degradation of the drug occurs within one week of opening the bottle, which further complicates this delivery approach. This paper focuses on designing a contact lens to treat the disease with improved efficacy compared to eye drops, and also exploring safety of the drug eluding contact lens in an animal model...
December 4, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29214524/effect-of-storage-conditions-on-stability-of-ophthalmological-compounded-cysteamine-eye-drops
#6
Ahmed Reda, Ann Van Schepdael, Erwin Adams, Prasanta Paul, David Devolder, Mohamed A Elmonem, Koenraad Veys, Ingele Casteels, Lambertus van den Heuvel, Elena Levtchenko
Cystinosis is a hereditary genetic disease that results in the accumulation of cystine crystals in the lysosomes, leading to many clinical manifestations. One of these manifestations is the formation of corneal cystine crystals, which can cause serious ocular complications. The only available drug to treat cystinosis is cysteamine, which breaks cystine and depletes its accumulation in the lysosomes. However, the oral form of cysteamine is not effective in treating corneal manifestations. Thus, ophthalmic solutions of cysteamine are applied...
December 7, 2017: JIMD Reports
https://www.readbyqxmd.com/read/29208977/protein-structure-insights-into-the-bilayer-interactions-of-the-saposin-like-domain-of-solanum-tuberosum-aspartic-protease
#7
Brian C Bryksa, Rickey Y Yada
Many plant aspartic proteases contain a saposin-like domain whose principal functions are intracellular sorting and host defence. Its structure is characterised by helical segments cross-linked by three highly conserved cystines. The present study on the saposin-like domain of Solanum tuberosum aspartic protease revealed that acidification from inactive to active conditions causes dimerisation and a strand-to-helix secondary structure transition independent of bilayer interaction. Bilayer fusion was shown to occur under reducing conditions yielding a faster shift to larger vesicle sizes relative to native conditions, implying that a lower level structural motif might be bilayer-active...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29204679/gestational-exposure-to-inorganic-arsenic-ias3-alters-glutamate-disposition-in-the-mouse-hippocampus-and-ionotropic-glutamate-receptor-expression-leading-to-memory-impairment
#8
Janikua Nelson-Mora, Martha L Escobar, Luis Rodríguez-Durán, Lourdes Massieu, Teresa Montiel, Verónica M Rodríguez, Karina Hernández-Mercado, María E Gonsebatt
Early life exposure to environmental pollutants and toxic chemicals has been linked to learning and behavioral alterations in children. iAs exposure is associated with different types neurological disorders such as memory and learning impairment. iAs is methylated in the brain by the arsenic III-methyltransferase in a process that requires glutathione (GSH). The xCT-antiporter cell membrane transporter participates in the influx of cystine for GSH synthesis in exchange for glutamate in a 1:1 ratio. In CD-1 mice gestationally exposed to 20 ppm of sodium arsenite in drinking water, we have previously observed up-regulation of xCT in the male mouse hippocampus which caused glutamatergic synapse alterations affecting learning and memory processes...
December 4, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29197934/effects-of-statin-treatment-with-atorvastatin-on-urolithiasis-associated-urinary-metabolic-risk-factors-an-experimental-study
#9
Mustafa Zafer Temiz, Emrah Yuruk, Kasim Ertas, Oguzhan Zengi, Atilla Semercioz
PURPOSE: To investigate whether atorvastatin has favorable effects on urinary metabolic risk factors associated with urolithiasis. METHODS: Sixteen male Sprague-Dawley rats were randomly divided into two groups, and baseline spot and 24-h urine samples were collected. Distilled water and atorvastatin were administered to rats during 4 weeks in the control and atorvastatin groups, respectively. At the end of the experimental procedure, spot and 24-h urine samples were collected again...
December 2, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29179563/clinical-outcomes-for-cystinuria-patients-with-unilateral-versus-bilateral-cystine-stone-disease
#10
Manint Usawachintachit, Benjamin Sherer, Matthew Hudnall, David T Tzou, Kazumi Taguchi, Ryan S Hsi, Marshall Stoller, Thomas Chi
<b>Introduction</b>: Cystinuria is a genetic disorder marked by elevated urinary cystine excretion and recurrent cystine nephrolithiasis. Interestingly, despite seemingly similar contralateral renal anatomy, a subset of cystinuric patients consistently form stones in only one kidney. The aim of this study is to evaluate clinical outcomes in unilateral versus bilateral cystine stone formers. <b>Methods</b>: We performed a retrospective case-control study of cystinuric patients evaluated and treated at the University of California, San Francisco between 1994 and 2015 and categorized patients as either unilateral or bilateral stone formers...
November 27, 2017: Journal of Endourology
https://www.readbyqxmd.com/read/29167447/hyperoxidation-of-ether-linked-phospholipids-accelerates-neutrophil-extracellular-trap-formation
#11
Satoshi Yotsumoto, Yuito Muroi, Tatsuya Chiba, Rio Ohmura, Maki Yoneyama, Megumi Magarisawa, Kosuke Dodo, Naoki Terayama, Mikiko Sodeoka, Ryohei Aoyagi, Makoto Arita, Satoko Arakawa, Shigeomi Shimizu, Masato Tanaka
Because neutrophil extracellular trap (NET) formation is involved in the pathology of a wide variety of diseases, NET-regulating compounds are expected to be useful for the therapies of these diseases. In this study, we identified sulfasalazine (SSZ) as a potent enhancer of NET formation both in vitro and in vivo. Although SSZ did not increase the amount of ROS generated, it accelerated the generation of ether-linked oxidized phospholipids, such as PE (18;1e/15-HETE) and PC (16;0e/13-HODE). Trolox, but not 2-ME, effectively suppressed lipid oxidation and NET formation that were induced by SSZ...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29154397/effects-of-high-ambient-temperature-on-plasma-metabolomic-profiles-in-chicks
#12
Shozo Tomonaga, Hirofumi Okuyama, Tetsuya Tachibana, Ryosuke Makino
Exposure to high ambient temperature is detrimental to the poultry industry. To understand the influence from a metabolic perspective, we investigated the effects of exposure to high ambient temperature on plasma low-molecular-weight metabolite levels in chicks using gas chromatography/mass spectrometry-based non-targeted metabolomic analysis. Heat exposure for 4 days suppressed growth and food intake. Of the 92 metabolites identified, the levels of 29 decreased, whereas the levels of nine increased. We performed an enrichment analysis on the identified metabolites and found 35 candidates for metabolic processes affected by heat exposure...
November 20, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/29145836/clinical-utility-of-computed-tomography-hounsfield-characterization-for-percutaneous-nephrolithotomy-a-cross-sectional-study
#13
Andrea Gallioli, Elisa De Lorenzis, Luca Boeri, Maurizio Delor, Stefano Paolo Zanetti, Fabrizio Longo, Alberto Trinchieri, Emanuele Montanari
BACKGROUND: Computed Tomography (CT) is considered the gold-standard for the pre-operative evaluation of urolithiasis. However, no Hounsfield (HU) variable capable of differentiating stone types has been clearly identified. The aim of this study is to assess the predictive value of HU parameters on CT for determining stone composition and outcomes in percutaneous nephrolithotomy (PCNL). METHODS: Seventy seven consecutive cases of PCNL between 2011 and 2016 were divided into 4 groups: 40 (52%) calcium, 26 (34%) uric acid, 5 (6%) struvite and 6 (8%) cystine stones...
November 16, 2017: BMC Urology
https://www.readbyqxmd.com/read/29139156/characterization-of-cysteine-thiol-modifications-based-on-protein-microenvironments-and-local-secondary-structures
#14
Akshay Bhatnagar, Debashree Bandyopadhyay
We have demonstrated earlier that protein microenvironments were conserved around disulphide-bridged cystine motifs with similar functions, irrespective of diversity in protein sequences (Bhatnagar et al., 2016; 84:1576-1589) . Here, cysteine thiol modifications were characterized based on protein microenvironments, secondary structures and specific protein functions. Protein microenvironment around an amino acid was defined as the summation of hydrophobic contributions from the surrounding protein fragments and the solvent molecules present within its first contact shell (Bandyopadhyay and Mehler, Proteins 2008; 72:646-659)...
November 15, 2017: Proteins
https://www.readbyqxmd.com/read/29136213/knottin-the-database-of-inhibitor-cystine-knot-scaffold-after-10-years-toward-a-systematic-structure-modeling
#15
Guillaume Postic, Jérôme Gracy, Charlotte Périn, Laurent Chiche, Jean-Christophe Gelly
Knottins, or inhibitor cystine knots (ICKs), are ultra-stable miniproteins with multiple applications in drug design and medical imaging. These widespread and functionally diverse proteins are characterized by the presence of three interwoven disulfide bridges in their structure, which form a unique pseudoknot. Since 2004, the KNOTTIN database (www.dsimb.inserm.fr/KNOTTIN/) has been gathering standardized information about knottin sequences, structures, functions and evolution. The website also provides access to bibliographic data and to computational tools that have been specifically developed for ICKs...
November 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29133937/stones-predicting-stone-episodes-using-cystine-capacity
#16
Matthew Bultitude, Kay Thomas
No abstract text is available yet for this article.
November 14, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29112493/-cysteamine-ophthalmic-hydrogel-for-the-treatment-of-ocular-cystinosis
#17
Anxo Fernández-Ferreiro, Andrea Luaces-Rodríguez, Victoria Díaz-Tomé, María Gil-Martínez, María Teresa Rodríguez Ares, Rosario Touriño Peralba, José Blanco-Méndez, Miguel González-Barcia, Francisco Javier Otero-Espinar, María Jesús Lamas
Ocular cystinosis is a rare disease characterised by the deposit of cystine crystals on the corneal surface, which hinder patients' eyesight. Oral cysteamine is given as cysteamine; however, it does not reach the cornea due to the lack of corneal vascularization making necessary its  administration by the topical ocular route. The aim of the present study is to  determine the stability of an ophthalmic hydrogel of cysteamine, which can be  potentially prepared at hospital pharmacy departments, under different preservation conditions during a follow-up of 30 days...
November 1, 2017: Farmacia Hospitalaria
https://www.readbyqxmd.com/read/29110985/cyclotides-a-versatile-ultrastable-micro-protein-scaffold-for-biotechnological-applications
#18
REVIEW
Julio A Camarero
Cyclotides are fascinating microproteins (≈30-40 residues long) with a unique head-to-tail cyclized backbone, stabilized by three disulfide bonds forming a cystine knot. This unique topology makes them exceptionally stable to chemical, thermal and biological degradation compared to other peptides of similar size. Cyclotides have been also found to be highly tolerant to sequence variability, aside from the conserved residues forming the cystine knot, able to cross cellular membranes and modulate intracellular protein-protein interactions both in vitro and in vivo...
October 21, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29109275/engineering-of-a-membrane-triggered-activity-switch-in-coagulation-factor-viia
#19
Anders L Nielsen, Anders B Sorensen, Heidi L Holmberg, Prafull S Gandhi, Johan Karlsson, Jens Buchardt, Kasper Lamberth, Mads Kjelgaard-Hansen, Carsten Dan Ley, Brit B Sørensen, Wolfram Ruf, Ole H Olsen, Henrik Østergaard
Recombinant factor VIIa (FVIIa) variants with increased activity offer the promise to improve the treatment of bleeding episodes in patients with inhibitor-complicated hemophilia. Here, an approach was adopted to enhance the activity of FVIIa by selectively optimizing substrate turnover at the membrane surface. Under physiological conditions, endogenous FVIIa engages its cell-localized cofactor tissue factor (TF), which stimulates activity through membrane-dependent substrate recognition and allosteric effects...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29108577/functionalization-of-mesoporous-organosilica-nanocarrier-for-ph-glutathione-dual-responsive-drug-delivery-and-imaging-of-cancer-therapy-process
#20
Lin-Lin Hu, Jie Meng, Dan-Dan Zhang, Ming-Li Chen, Yang Shu, Jian-Hua Wang
A multifunctional drug nanocarrier is developed by incorporating acetaldehyde-modified-cystine (AMC) into mesoporous organosilica nanoparticles (MONs), shortly termed as MONs-AMC. The anticancer drug doxorubicin (DOX) links directly to MONs-AMC through electrostatic interaction between DOX and AMC to produce a conjugate, MONs-AMC-DOX, with a drug loading efficiency of 26.24 ± 1.35%, corresponding to a loading capacity of 0.26 ± 0.01mgmg(-1) for DOX. Schiff base AMC contains a -S-S- bond and two -C˭N- bonds which cleave in the presence of certain level of GSH and in an acidic medium, providing MONs-AMC-DOX the capability for triggering pH and glutathione (GSH) dual-responsive drug release...
January 15, 2018: Talanta
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