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Lucas C Wheeler, Micah T Donor, James S Prell, Michael J Harms
The S100 proteins are a large family of signaling proteins that play critical roles in biology and disease. Many S100 proteins bind Zn2+, Cu2+, and/or Mn2+ as part of their biological functions; however, the evolutionary origins of binding remain obscure. One key question is whether divalent transition metal binding is ancestral, or instead arose independently on multiple lineages. To tackle this question, we combined phylogenetics with biophysical characterization of modern S100 proteins. We demonstrate an earlier origin for established S100 subfamilies than previously believed, and reveal that transition metal binding is widely distributed across the tree...
2016: PloS One
Kateki Vinod, Steven J Gedde
PURPOSE OF REVIEW: This article reviews recent studies evaluating the efficacy and complication profiles of novel glaucoma procedures promoting aqueous outflow. RECENT FINDINGS: Literature from the 2015 to 2016 review period includes abundant data regarding new and emerging glaucoma procedures. Notable findings from recent randomized clinical trials include titratability of intraocular pressure with multiple trabecular microbypass stents (iStent; Glaukos, Laguna Hills, California, USA) and greater reduction in intraocular pressure and medication usage following intracanalicular scaffolding (Hydrus Microstent; Ivantis Inc...
October 19, 2016: Current Opinion in Ophthalmology
Ross Beaumont, Philip Cordery, Mark Funnell, Stephen Mears, Lewis James, Phillip Watson
This study examined effects of 4 weeks of caffeine supplementation on endurance performance. Eighteen low-habitual caffeine consumers (<75 mg · day(-1)) were randomly assigned to ingest caffeine (1.5-3.0 mg · kg(-1)day(-1); titrated) or placebo for 28 days. Groups were matched for age, body mass, V̇O2peak and Wmax (P > 0.05). Before supplementation, all participants completed one V̇O2peak test, one practice trial and 2 experimental trials (acute 3 mg · kg(-1) caffeine [precaf] and placebo [testpla])...
October 20, 2016: Journal of Sports Sciences
Sujin Seo, Huiyeong Ju, Seulgi Kim, In-Hyeok Park, Eunji Lee, Shim Sung Lee
Homo- and heteronuclear group 12 metal (Zn(2+), Cd(2+), and Hg(2+)) complexes 1-6 containing a newly designed 18-membered N2O2S2 macrocycle incorporating two pyridine subunits (L) were prepared and structurally characterized. The individual complexes isolated exhibit unusual stoichiometries, geometries, oxidation states, and structural topologies and include an infinite mercurous complex and a heteronuclear dumbbell-shaped complex. Both the Zn(II) complex [Zn(L)][ZnBr4] (1) and the Cd(II) complex [Cd(L)Br2] (2) are mononuclear, with the metal ion located inside the macrocyclic cavity...
October 20, 2016: Inorganic Chemistry
D Stott, M Bolten, D Paraschiv, I Papastefanou, J B Chambers, N A Kametas
OBJECTIVE: Pregnant hypertensive women who do not respond to labetalol but need vasodilatory therapy for blood pressure (BP) control rapidly progress to severe disease, which may be delayed by early recognition and individualised BP treatment. In this study, we sought to create prediction models at presentation, at 1 and 24 hours after commencement of treatment to identify patients who will not show a sustained response to labetalol and therefore need vasodilatory therapy. METHODS: The study population comprised of 134 women presenting with hypertension at a UK hospital...
October 20, 2016: Ultrasound in Obstetrics & Gynecology
Subhadeep Saha, Aditi Roy, Kanak Roy, Mahendra Nath Roy
Host-guest inclusion complexes of β-cyclodextrin with two vitamins viz., nicotinic acid and ascorbic acid in aqueous medium have been explored by reliable spectroscopic, physicochemical and calorimetric methods as stabilizer, carrier and regulatory releaser of the guest molecules. Job's plots have been drawn by UV-visible spectroscopy to confirm the 1:1 stoichiometry of the host-guest assembly. Stereo-chemical nature of the inclusion complexes has been explained by 2D NMR spectroscopy. Surface tension and conductivity studies further support the inclusion process...
October 20, 2016: Scientific Reports
Valeria Lanza, Alessio Travaglia, Gaetano Malgieri, Roberto Fattorusso, Giuseppe Grasso, Giuseppe Di Natale, Valeria Zito, Giuseppe Arena, Danilo Milardi, Enrico Rizzarelli
Many biochemical pathways involving nerve growth factor (NGF), a neurotrophin with copper(II) binding abilities, are regulated by the ubiquitin (Ub) proteasome system. However, whether NGF binds Ub and the role played by copper(II) ions in modulating their interactions have not yet been investigated. Herein NMR spectroscopy, circular dichroism, ESI-MS, and titration calorimetry are employed to characterize the interactions of NGF with Ub. NGF1-14 , which is a short model peptide encompassing the first 14 N-terminal residues of NGF, binds the copper-binding regions of Ub (KD =8...
October 19, 2016: Chemistry: a European Journal
Dong-Liang Chen, Yu-Hong Li, Zhi-Juan Wang, Ye-Ke Zhu
Gabapentin has been used as an adjuvant for treatment of cancer pain. Previous studies showed that opioids combined with gabapentin for management of cancer pain reduced the dosage of opioids.The objective of this study was to explore the clinical effect and patients' satisfaction of oxycontin combined with gabapentin in treatment of severe cancer pain. After titration of morphine, 60 severe cancer patients with visual analog score (VAS) more than 7 were randomly divided into trial group (n = 30) and control group (n = 30)...
October 2016: Medicine (Baltimore)
Rajkumar Bharatia, Manoj Chitale, Ganesh Narain Saxena, Raman Ganesh Kumar, Chikkalingaiah, Abhijit Trailokya, Kalpesh Dalvi, Suhas Talele
INTRODUCTION: Hypertension (HTN), being a major risk factor for cardiovascular diseases (CVDs), is an important issue of medical and public health. High blood pressure (BP) is ranked as the third most important risk factor for attributable burden of disease in south Asia (2010). Hypertension (HTN) exerts a substantial public health burden on cardiovascular health status and healthcare systems in India. Uncontrolled hypertension among adults with hypertension is associated with increased mortality...
July 2016: Journal of the Association of Physicians of India
Sree Vamsee Chintapalli, Srinivas Jayanthi, Prema L Mallipeddi, Ravi Kumar Gundampati, Suresh Kumar Thallapuranam Krishnaswamy, Damian B van Rossum, Andriy Anishkin, Sean H Adams
Previous research has indicated that long-chain fatty acids can bind myoglobin (Mb) in an oxygen dependent manner. This suggests that Oxy-Mb may play an important role in fuel delivery in Mb-rich muscle fibers (e.g., type I fibers and cardiomyocytes), and raises the possibility that Mb also serves as an acylcarnitine binding protein. We report for the first time the putative interaction and affinity characteristics for different chain lengths of both fatty acids and acylcarnitines with Oxy-Mb using molecular dynamic simulations and isothermal titration calorimetry experiments...
October 7, 2016: Journal of Biological Chemistry
Heiko Ihmels, Katy Schäfer, Giampietro Viola, Elena Porcu
The interactions of 8-hydroxybenzo[b]quinolizinium and 9-hydroxy-benzo[b]quinolizinium with DNA are investigated in detail. Specifically, spectro¬photometric and spectrofluorimetric titrations, thermal DNA-de¬na¬turation experiments as well as CD- and LD-spectroscopic ana¬lysis show that a pH shift by just one or two orders of magnitude has a significant impact on the interactions of the acidic ligands with the nucleic acid. Both ligands bind with high affinity to DNA at pH = 6 (Kb ≈ 105 M-1). At pH = 7 or 8, however, the binding interactions are much weaker because of the formation of the corresponding charge neutral conjugate bases whose affinity to DNA is reduced due to the resulting lack of a positive charge...
October 19, 2016: Chemistry: a European Journal
Mengqi Lv, Chongyuan Wang, Fudong Li, Junhui Peng, Bin Wen, Qingguo Gong, Yunyu Shi, Yajun Tang
Mitophagy is an essential intracellular process that eliminates dysfunctional mitochondria and maintains cellular homeostasis. Mitophagy is regulated by the post-translational modification of mitophagy receptors. Fun14 domain-containing protein 1 (FUNDC1) was reported to be a new receptor for hypoxia-induced mitophagy in mammalian cells and interact with microtubule-associated protein light chain 3 beta (LC3B) through its LC3 interaction region (LIR). Moreover, the phosphorylation modification of FUNDC1 affects its binding affinity for LC3B and regulates selective mitophagy...
October 18, 2016: Protein & Cell
Andrés Corral Lugo, Abdelali Daddaoua, Alvaro Ortega, Bertrand Morel, Ana Isabel Díez Peña, Manuel Espinosa-Urgel, Tino Krell
Quorum sensing systems are essential for bacterial communication. We report here the purification and characterization of the Pseudomonas aeruginosa LasR quorum sensing regulator purified from lysates of E. coli cultures grown in the absence of added acyl-homoserine lactones (AHL). We show by isothermal titration calorimetry that LasR recognizes different AHLs with an affinity of approximately 1 μM. The affinity of LasR for its cognate 3-Oxo-C12-AHL was similar to that of other AHLs, indicating that this regulator has not evolved to preferentially recognize its cognate AHL...
October 15, 2016: Protein Expression and Purification
Christopher P Lawrance, Matthew C Henn, Jacob R Miller, Michael A Kopek, Andrew J Zhang, Richard B Schuessler, Ralph J Damiano
BACKGROUND: Atrial fibrillation (AF) occurs in 30% of patients with mitral regurgitation referred for surgical intervention. However, the underlying mechanisms in this population are poorly understood. This study examined the effects of acute left atrial volume overload on atrial electrophysiology and the inducibility of AF. METHODS: Ten canines underwent insertion of an atrioventricular shunt between the left ventricle and left atrium. Shunt and aortic flows were calculated, and the shunt was titrated to a shunt fraction to 40% to 50% of cardiac output...
October 15, 2016: Annals of Thoracic Surgery
Anthony G Messina, Michael Wang, Marshall J Ward, Chase C Wilker, Brett B Smith, Daniel P Vezina, Nathan Leon Pace
BACKGROUND: General anaesthesia is usually associated with unconsciousness. 'Awareness' is when patients have postoperative recall of events or experiences during surgery. 'Wakefulness' is when patients become conscious during surgery, but have no postoperative recollection of the period of consciousness. OBJECTIVES: To evaluate the efficacy of two types of anaesthetic interventions in reducing clinically significant awareness:- anaesthetic drug regimens; and- intraoperative anaesthetic depth monitors...
October 18, 2016: Cochrane Database of Systematic Reviews
Nazanin Ebrahimiadib, Bobeck S Modjtahedi, Samaneh Davoudi, C Stephen Foster
PURPOSE: To evaluate the efficacy of chlorambucil in the treatment of serpiginous choroiditis. METHODS: Patient records from the Massachusetts Eye Research and Surgery Institution (MERSI) were reviewed from over the past 10 years. In total, 17 patients with the diagnosis of serpiginous choroiditis treated with chlorambucil were identified. QuantiFERON gold was negative in all of them. Chlorambucil was started at 0.15 mg/kg and dosage was titrated up using weekly white blood cell (WBC) count to achieve a target cell number of 3...
October 18, 2016: Ocular Immunology and Inflammation
Julie M Waldfogel, Suzanne Nesbit, Steven P Cohen, Sydney M Dy
Opioids remain the mainstay of treatment for severe cancer pain, but up to 20% of patients have persistent or refractory pain despite rapid and aggressive opioid titration, or develop refractory pain after long-term opioid use. In these scenarios, alternative agents and mechanisms for analgesia should be considered. This case report describes a 28-year-old man with metastatic pancreatic neuroendocrine cancer with severe, intractable pain despite high-dose opioids including methadone and a hydromorphone patient-controlled analgesia (PCA)...
October 18, 2016: Journal of Pain & Palliative Care Pharmacotherapy
Naoki Nakagawa, Keisuke Maruyama, Motoki Matsuki, Nobuyuki Sato, Kenjiro Kikuchi, Naoyuki Hasebe
OBJECTIVE: Uric acid is a risk factor for cardiovascular disease. We investigated the relationship between the change of urinary albumin excretion (UAE) and the changes of serum uric acid (SUA) during antihypertensive treatment in hypertensive patients with microalbuminuria as a subanalysis of the results of the NICE Combi (Nifedipine and Candesartan Combination) Study. DESIGN AND METHOD: A total of 86 subjects with essential hypertension with microalbuminuria (UAE < 300 mg•g-1 creatinine) were randomly assigned in a double-blind manner to a combination therapy group (standard-dose candesartan at 8 mg/day plus controlled-release (CR) nifedipine 20 mg/day) (n = 42) or an up-titrated monotherapy group (candesartan 12 mg/day) (n = 44) for 8 weeks of continuous treatment after initially receiving standard-dose candesartan (8 mg/day) monotherapy for 8 weeks (initial treatment)...
September 2016: Journal of Hypertension
Ruixin Ma, Qiongying Wang, Ningyin Li, Yang Zhao, Xu Zhao, Heng Yu, Jing Yu
OBJECTIVE: Home blood pressure monitoring (HBPM) is more likely to reflect the patient's underlying blood pressure (BP), than measurements in the clinic. HBPM coupled with titration of medications under the guidance of doctors, is a viable intervention to control hypertension. The purpose of this study is to evaluate whether HBPM can increase the safety of the combination therapy of three or more different classes of antihypertensive drugs. DESIGN AND METHOD: We enrolled patients with severe (grade 3) hypertension, whose BP remain uncontrolled under combination treatment with standard doze of an angiotensin II receptor blocker and hydrochlorothiazide...
September 2016: Journal of Hypertension
Masaaki Sugiyama, Hirokazu Yagi, Kentaro Ishii, Lionel Porcar, Anne Martel, Katsuaki Oyama, Masanori Noda, Yasuhiro Yunoki, Reiko Murakami, Rintaro Inoue, Nobuhiro Sato, Yojiro Oba, Kazuki Terauchi, Susumu Uchiyama, Koichi Kato
The molecular machinery of the cyanobacterial circadian clock consists of three proteins: KaiA, KaiB, and KaiC. Through interactions among the three Kai proteins, the phosphorylation states of KaiC generate circadian oscillations in vitro in the presence of ATP. Here, we characterized the complex formation between KaiB and KaiC using a phospho-mimicking mutant of KaiC, which had an aspartate substitution at the Ser431 phosphorylation site and exhibited optimal binding to KaiB. Mass-spectrometric titration data showed that the proteins formed a complex exclusively in a 6:6 stoichiometry, indicating that KaiB bound to the KaiC hexamer with strong positive cooperativity...
October 18, 2016: Scientific Reports
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