Oxalate Oxidase Model Studies – Substrate Reactivity

The synthesis and structure of [MnLCl]0.5H2O (1·0.5H2O, HL = 1‐benzyl‐4‐acetato‐1,4,7‐triazacyclononane) is reported. Complex 1 exists as a coordination polymer in the solid state, and the MnII center is bonded to three amine nitrogen atoms, one carboxylate oxygen atom, a chlorido ligand, and an adjacent carboxylate group in a chelating fashion to afford a seven‐coordinate center. The dissolution of 1 in acetonitrile containing excess oxalate (ox) ions results in a monomeric species. When mixtures of 1 and oxalate ions are exposed to oxygen under ambient conditions, a dark pink EPR‐silent species is generated. The pink species is believed to be [MnIII(ox)2]–, which results from the displacement of the ligand L– by an oxalate ion. The decomposition of this species ultimately results in the formation of 1 equiv. of CO2 per oxalate ion consumed, a HCO3– ion, and a MnII species. Further reaction of the resulting MnII species with excess oxalate in the presence of oxygen leads to additional oxalate degradation.MnLCl (HL = 1‐benzyl‐4‐acetato‐1,4,7‐triazacyclononane) is investigated as a structural and functional model for oxalate oxidase. MnLCl effects the catalytic degradation of oxalate ions under ambient conditions. MnLCl is converted to a light‐sensitive intermediate during catalysis. Analysis of the reaction mixture indicates that 1 equiv. of CO2 per oxalate ion is produced along with a HCO3– ion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110613/1/646_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110613/2/ejic_201402835_sm_miscellaneous_information.pd

Challenging assumptions of the enlargement literature : the impact of the EU on human and minority rights in Macedonia

This article argues that from the very start of the transition process in Macedonia, a fusion of concerns about security and democratisation locked local nationalist elites and international organisations intoa political dynamic that prioritised security over democratisation. This dynamic resulted in little progress in the implementation of human and minority rights until 2009, despite heavy EU involvement in Macedonia after the internal warfare of 2001. The effects of this informally institutionalised relationship have been overlooked by scholarship on EU enlargement towards Eastern Europe, which has made generalisations based on assumptions relevant to the democratisation of countries in Eastern Europe, but not the Western Balkans

Synthesis of Some Dioxotungsten(VI) Chelates with 1,3- Diketones

The preparation of dioxotungsten (VI) chelates of the W02L 2 type with acetyJacetone and dibenzoylmethane is described ailld some properties of these chelates aTe discussed. The chelate with benzoylacetone has a structure apparently different from that of the two other chelates, as evidenced by the differences in the metal to Ligand ratio and by the infrared spectra

Our first experience in laparoscopic colorectal operations

Purpose: It has been almost 23 years since the first laparoscopic-assisted right hemicolectomy was done when the surgeons in our institution started doing laparoscopic colorectal operations mainly for malignant diseases. The aim of this communication was to present the beginning of the laparoscopic colorectal operations in St. Naum University Clinic of Surgical Diseases in Skopje, Macedonia.Material and methods: Twenty patients with colorectal adenocarcinoma were laparoscopically operated during the period from December 2012 to June 2013. Eleven of them were men and the rest women at a mean age of 58 years. Eight of them were rectal cancers, 3 were cancers of the rectosigmoid and the rest 9 were sigmoid adenocarcinomas. The patients were operated with 4 ports (sigmoid cancer) and 5 ports (rectum). Medial-to-lateral approach was used in all the cases. Tumour location dictated whether high or low ligation of inferior mesenteric artery (IMA) was done. Double stapler technique was applied for distal resection and anastomosis creation.Results: Mean operating time was 315 min. There were no perioperative and early postoperative deaths. One patient was reoperated early at the same operating day for mesenteric venous bleeding. There was one case of anastomotic leakage and a laparotomy was done with temporary colostomy. One unit of blood was given to five patients due to perioperative bleeding. Mean length of hospital stay was six days. Per oral nutrition started at day 2. Mean bowel function returned after 3,5 days. There were two seromas of the minilaparotomy wounds and no cases of surgical site infection. Selected cases of sigmoid and rectal cancer were suitable for beginning of learning the laparoscopic colorectal resection technique. The long operating time was understandable due to the steep learning curve. Conclusion: Laparoscopic colorectal surgery is safe and oncologically routine surgical method. It is widely used for many benign colorectal diseases, too. Prolonged learning of this technique should not be discouraging

Multidimentional proteomics for cell biology

The proteome is a dynamic system in which each protein has interconnected properties — dimensions — that together contribute to the phenotype of a cell. Measuring these properties has proved challenging owing to their diversity and dynamic nature. Advances in mass spectrometry-based proteomics now enable the measurement of multiple properties for thousands of proteins, including their abundance, isoform expression, turnover rate, subcellular localization, post-translational modifications and interactions. Complementing these experimental developments are new data analysis, integration and visualization tools as well as data-sharing resources. Together, these advances in the multidimensional analysis of the proteome are transforming our understanding of various cellular and physiological processes

Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson’s Disease

Parkinson’s disease (PD) is a chronic, age-related, progressive multisystem disease associated with neuroinflammation and immune dysfunction. This review discusses the methodological approaches used to study the changes in central and peripheral immunity in PD, the advantages and limitations of the techniques, and their applicability to humans. Although a single animal model cannot replicate all pathological features of the human disease, neuroinflammation is present in most animal models of PD and plays a critical role in understanding the involvement of the immune system (IS) in the pathogenesis of PD. The IS and its interactions with different cell types in the central nervous system (CNS) play an important role in the pathogenesis of PD. Even though culture models do not fully reflect the complexity of disease progression, they are limited in their ability to mimic long-term effects and need validation through in vivo studies. They are an indispensable tool for understanding the interplay between the IS and the pathogenesis of this disease. Understanding the immune-mediated mechanisms may lead to potential therapeutic targets for the treatment of PD. We believe that the development of methodological guidelines for experiments with animal models and PD patients is crucial to ensure the validity and consistency of the results

Dispatcher-Assisted Cardiopulmonary Resuscitation — Influence on Return of Spontaneous Circulation and Short-Term Survival

The Aim: analysis of the influence of dispatcher assistance during cardiopulmonary resuscitation (CPR) of patients with out-of-hospital cardiac arrest (OHCA) in achieving return of spontaneous circulation (ROSC), better survival at the scene, survival to discharge, and 30-day survival.Materials and methods. This study includes epidemiological data on OHCA collected by the study protocol of the European Resuscitation Council's EuReCa_ONE study during the period October 1, 2014 — December 31, 2019. Statistical analysis was performed using SPSS Statistics v26 and GraphPad Prism v8 software packages.Results. This study included 288 patients with OHCA where CPR was provided by bystander. Dispatcher-assisted CPR (DA-CPR) occurred in 56.9% of those patients and ROSC was achieved in 31.3% of cases. Forty-four patients were hospitalized and 16 of those survived until discharge. There was no influence of dispatcher assistance on ROSC, although it resulted in slightly greater risk of the absence of ROSC (OR=1.063). Higher mortality rate to discharge occurred in DA-CPR group (P=0.013). No statistical significance was observed between DA-CPR and non-DA-CPR groups in terms of death at the scene, and 30-day survival. Dispatcher assistance during the initial CPR in hospitalized OHCA patients was a significant predictor of death outcome during hospitalization (P=0.017, OR=5.500).Conclusions. There is no significant association between the presence/absence of dispatcher assistance and ROSC or 30-day survival rate. In contrast, DA-CPR was non-significantly associated with slightly higher odds for the absence of ROSC. DA-CPR was also associated with lower survival-to-discharge rates in hospitalized OHCA patients. The study findings are the base/ground which highlights the need of implementation of existing and development of new guidelines regarding high-quality professional training of EMS dispatchers as well as basic life support education of general population

2002-2003 Florida\u27s Young Musician Showcase

https://spiral.lynn.edu/conservatory_otherseasonalconcerts/1090/thumbnail.jp

GHTD-amide : A naturally occurring beta cell-derived peptide with hypoglycemic activity

in the early 1970s, a peptide fraction with insulin potentiating activity was purified from human urine but the identity and origins of the active constituent remained unknown. Here we identify the active component and characterize its origins. The active peptide was identified as an alpha amidated tetrapeptide with the sequence GHTD-amide. The peptide was synthesized and tested for stimulation of glycogen synthesis and insulin potentiation by insulin tolerance testing in insulin-deficient rats, which confirmed GHTD-amide as the active peptide. Tissue localization using a peptide-specific anti-serum and epifluorescent and confocal microscopy showed decoration of pancreatic islets but not other tissues. Confocal microscopy revealed co-localization with insulin and immunogold and electron microscopy showed localization to dense core secretory granules. Consistent with these observations GHTD-amide was found in media conditioned by MIN6 islet beta cells. Sequence database searching found no annotated protein in the human proteome encoding a potential precursor for GHTD-amide. We conclude that the insulin potentiating activity originally described in human urine is attributable to the tetrapeptide GHTD-amide. GHTD-amide is a novel peptide produced by pancreatic beta cells and no precursor protein is present in the annotated human proteome. Stimulation of glycogen synthesis and co-localization with insulin in beta cells suggest that GHTD-amide may play a role in glucose homeostasis by enhancing insulin action and glucose storage in tissues. (C) 2008 Elsevier Inc. All rights reserved

Two Tryptophans Are Better Than One in Accelerating Electron Flow through a Protein

We have constructed and structurally characterized a <i>Pseudomonas aeruginosa</i> azurin mutant <b>Re126WWCu^I</b>, where two adjacent tryptophan residues (W124 and W122, indole separation 3.6–4.1 Å) are inserted between the Cu^I center and a Re photosensitizer coordinated to the imidazole of H126 (Re^I(H126)­(CO)₃(4,7-dimethyl-1,10-phenanthroline)⁺). Cu^I oxidation by the photoexcited Re label (*Re) 22.9 Å away proceeds with a ∼70 ns time constant, similar to that of a single-tryptophan mutant (∼40 ns) with a 19.4 Å Re–Cu distance. Time-resolved spectroscopy (luminescence, visible and IR absorption) revealed two rapid reversible electron transfer steps, W124 → *Re (400–475 ps, <i>K</i>₁ ≅ 3.5–4) and W122 → W124^•+ (7–9 ns, <i>K</i>₂ ≅ 0.55–0.75), followed by a rate-determining (70–90 ns) Cu^I oxidation by W122^•+ ca. 11 Å away. The photocycle is completed by 120 μs recombination. No photochemical Cu^I oxidation was observed in <b>Re126FWCu^I</b>, whereas in <b>Re126WFCu^I</b>, the photocycle is restricted to the ReH126W124 unit and Cu^I remains isolated. QM/MM/MD simulations of <b>Re126WWCu^I</b> indicate that indole solvation changes through the hopping process and W124 → *Re electron transfer is accompanied by water fluctuations that tighten W124 solvation. Our finding that multistep tunneling (hopping) confers a ∼9000-fold advantage over single-step tunneling in the double-tryptophan protein supports the proposal that hole-hopping through tryptophan/tyrosine chains protects enzymes from oxidative damage