Faculty Opinions recommendation of De novo-designed metallopeptides with type 2 copper centers: modulation of reduction potentials and nitrite reductase activities.

2013 ◽  
Author(s):  
Dan Kosman
Keyword(s):  
Nitrite Reductase ◽  
De Novo ◽  
Reduction Potentials

scholarly journals Disease course of Neurofibromatosis Type 2; a 30-year follow-up study of 353 patients seen at a single institution

2020 ◽  
Author(s):  
Claire Forde ◽  
Andrew T King ◽  
Scott A Rutherford ◽  
Charlotte Hammerbeck-Ward ◽  
Simon K Lloyd ◽  
...  
Keyword(s):  
De Novo ◽  
Radiation Treatment ◽  
Univariate Analysis ◽  
Age At Onset ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Disease Course ◽  
Number Of Patients

Abstract Background Limited data exists on the disease course of Neurofibromatosis Type 2 (NF2) to guide clinical trial design. Methods A prospective database of patients meeting NF2 diagnostic criteria, reviewed between 1990–2020, was evaluated. Follow-up to first vestibular schwannoma (VS) intervention and death was assessed by univariate analysis and stratified by age at onset, era referred and inheritance type. Interventions for NF2-related tumours were assessed. Cox regression was performed to determine the relationship between individual factors from time of diagnosis to NF2-related death. Results Three-hundred-and-fifty-three patients were evaluated. During 4643.1 follow-up years from diagnosis to censoring 60 patients (17.0%) died. The annual mean number of patients undergoing VS surgery or radiotherapy declined, from 4.66 and 1.65 respectively per 100 NF2 patients in 1990-1999 to 2.11 and 1.01 in 2010-2020, as the number receiving bevacizumab increased (2.51 per 100 NF2 patients in 2010-2020). Five patients stopped bevacizumab to remove growing meningioma or spinal schwannoma. 153/353 (43.3%) had at least one neurosurgical intervention/radiation treatment within 5 years of diagnosis. Patients asymptomatic at diagnosis had longer time to intervention and better survival compared to those presenting with symptoms. Those symptomatically presenting <16 and >40 years had poorer overall survival than those presenting at 26-39 years (P=0.03 and P=0.02 respectively) but those presenting between 16-39 had shorter time to VS intervention. Individuals with de novo constitutional variants had worse survival than those with de novo mosaic or inherited disease (P=0.004). Conclusion Understanding disease course improves prognostication, allowing for better informed decisions about care.

scholarly journals CNNM2-Related Disorders: Phenotype and Its Severity Were Associated With the Mode of Inheritance

2021 ◽  
Vol 9 ◽  
Author(s):  
Han Zhang ◽  
Ye Wu ◽  
Yuwu Jiang
Keyword(s):  
De Novo ◽  
Serum Magnesium ◽  
Brain Magnetic Resonance Imaging ◽  
Functional Studies ◽  
Pathogenic Variants ◽  
Significant Difference ◽  
Domain Variations ◽  
Type 3

CNNM2 (Cystathionine-β-synthase-pair Domain Divalent Metal Cation Transport Mediator 2) pathogenic variants have been reported to cause hypomagnesemia, epilepsy, and intellectual disability/developmental delay (ID/DD). We identified two new cases with CNNM2 novel de novo pathogenic variants, c.814T>C and c.976G>C. They both presented with infantile-onset epilepsy with DD and hypomagnesemia refractory to magnesium supplementation. To date, 21 cases with CNNM2-related disorders have been reported. We combined all 23 cases to analyze the features of CNNM2-related disorders. The phenotypes can be classified into three types: type 1, autosomal dominant (AD) inherited simple hypomagnesemia; type 2, AD inherited hypomagnesemia with epilepsy and ID/DD; and type 3, autosomal recessive (AR) inherited hypomagnesemia with epilepsy and ID/DD. All five type 1 cases had no epilepsy or ID/DD; they all had hypomagnesemia, and three of them presented with symptoms secondary to hypomagnesemia. Fifteen type 2 patients could have ID/DD and seizures, which can be controlled with antiseizure medications (ASMs); their variations clustered in the DUF21 domain of CNNM2. All three type 3 patients had seizures from 1 to 6 days after birth; the seizures were refractory, and 1/3 had status epilepticus; ID/DD in these AR-inherited cases was more severe than that of AD-inherited cases; they all had abnormalities of brain magnetic resonance imaging (MRI). Except for one patient whose serum magnesium was the lower limit of normal, others had definite hypomagnesemia. Hypomagnesemia could be improved after magnesium supplement but could not return to the normal level. Variations in the CBS2 domain may be related to lower serum magnesium. However, there was no significant difference in the level of serum magnesium among the patients with three different types of CNNM2-related disorders. The severity of different phenotypes was therefore not explained by decreased serum magnesium. We expanded the spectrum of CNNM2 variants and classified the phenotypes of CNNM2-related disorders into three types. We found that DUF21 domain variations were most associated with CNNM2-related central nervous system phenotypes, whereas hypomagnesemia was more pronounced in patients with CBS2 domain variations, and AR-inherited CNNM2-related disorders had the most severe phenotype. These results provide important clues for further functional studies of CNNM2 and provide basic foundations for more accurate genetic counseling.

Fuzzy Goal Programming With Interval Type-2 for Solving Multi-Objective Sustainable Supplier Selection Problems

2021 ◽  
pp. 164-197
Author(s):  
Nurullah UMARUSMAN
Keyword(s):  
Supply Chain ◽  
Goal Programming ◽  
Supplier Selection ◽  
De Novo ◽  
Fuzzy Goal Programming ◽  
Multi Objective ◽  
Sustainable Supplier Selection ◽  
Fuzzy Goal ◽  
Interval Type

Supply chain management is going on changing and developing in line with the needs of the growing global supply chain. Performance of supply chain, considered as a whole so that businesses can accommodate these evolvements and change, needs to be improved in the long run. Actually, businesses work with suppliers complying with their policies from past to present. However, other dimensions of sustainability should be considered, as well as economic criteria when selecting suppliers. With the right supplier selection made in this respect, by contributing to the efficient functioning of the supply chain, it will increase customer satisfaction, and therefore, the enterprises will reach the goals they set. The solution of the multi-objective sustainable supplier selection problem has been realized by using the “satisfied optimal supplier design” algorithm, also called fuzzy goal programming, with de novo-based interval type-2 proposed in this study.

scholarly journals The Blue Copper-Containing Nitrite Reductase fromAlcaligenes xylosoxidans: Cloning of the nirAGene and Characterization of the Recombinant Enzyme

1999 ◽  
Vol 181 (8) ◽  
pp. 2323-2329 ◽  
Author(s):  
Miguel Prudêncio ◽  
Robert R. Eady ◽  
Gary Sawers
Keyword(s):  
Amino Acid ◽  
Nitrite Reductase ◽  
Recombinant Enzyme ◽  
Leader Peptide ◽  
Resonance Spectroscopy ◽  
Gene Encoding ◽  
Blue Copper

ABSTRACT The nirA gene encoding the blue dissimilatory nitrite reductase from Alcaligenes xylosoxidans has been cloned and sequenced. To our knowledge, this is the first report of the characterization of a gene encoding a blue copper-containing nitrite reductase. The deduced amino acid sequence exhibits a high degree of similarity to other copper-containing nitrite reductases from various bacterial sources. The full-length protein included a 24-amino-acid leader peptide. The nirA gene was overexpressed inEscherichia coli and was shown to be exported to the periplasm. Purification was achieved in a single step, and analysis of the recombinant Nir enzyme revealed that cleavage of the signal peptide occurred at a position identical to that for the native enzyme isolated from A. xylosoxidans. The recombinant Nir isolated directly was blue and trimeric and, on the basis of electron paramagnetic resonance spectroscopy and metal analysis, possessed only type 1 copper centers. This type 2-depleted enzyme preparation also had a low nitrite reductase enzyme activity. Incubation of the periplasmic fraction with copper sulfate prior to purification resulted in the isolation of an enzyme with a full complement of type 1 and type 2 copper centers and a high specific activity. The kinetic properties of the recombinant enzyme were indistinguishable from those of the native nitrite reductase isolated from A. xylosoxidans. This rapid isolation procedure will greatly facilitate genetic and biochemical characterization of both wild-type and mutant derivatives of this protein.

scholarly journals Circulating calcium levels and the risk of type 2 diabetes: a systematic review and meta-analysis

2019 ◽  
Vol 122 (04) ◽  
pp. 376-387 ◽  
Author(s):  
J. Zhu ◽  
P. Xun ◽  
J. C. Bae ◽  
J. H. Kim ◽  
D. J. Kim ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Cohort Studies ◽  
Glucose Homeostasis ◽  
De Novo ◽  
Meta Analysis ◽  
Cross Sectional ◽  
Relative Risks ◽  
Ca Homeostasis

AbstractAbnormal Ca homeostasis has been associated with impaired glucose metabolism. However, the epidemiological evidence is controversial. We aimed to assess the association between circulating Ca levels and the risk of type 2 diabetes mellitus (T2DM) or abnormal glucose homeostasis through conducting a systematic review and meta-analysis. Eligible studies were identified by searching electronic database (PubMed, Embase and Google Scholar) and related references withde novoresults from primary studies up to December 2018. A random-effects meta-analysis was performed to estimate the weighted relative risks (RR) and 95 % CI for the associations. The search yielded twenty eligible publications with eight cohort studies identified for the meta-analysis, which included a total of 89 165 participants. Comparing the highest with the lowest category of albumin-adjusted serum Ca, the pooled RR was 1·14 (95 % CI 1·05, 1·24) for T2DM (n51 489). Similarly, serum total Ca was associated with incident T2DM (RR 1·25; 95 % CI 1·10, 1·42) (n64 502). Additionally, the adjusted RR for 1 mg/dl increments in albumin-adjusted serum Ca or serum total Ca levels was 1·16 (95 % CI 1·07, 1·27) and 1·19 (95 % CI 1·11, 1·28), respectively. The observed associations remained with the inclusion of a cohort study with ionised Ca as the exposure. However, data pooled from neither case–control (n4) nor cross-sectional (n8) studies manifested a significant correlation between circulating Ca and glucose homeostasis. In conclusion, accumulated data from the cohort studies suggest that higher circulating Ca levels are associated with an augmented risk of T2DM.

scholarly journals Anabolic androgenic steroids exert a selective remodeling of the plasma lipidome that mirrors the decrease of the de novo lipogenesis in the liver

Metabolomics ◽  
2020 ◽  
Vol 16 (1) ◽  
Author(s):  
David Balgoma ◽  
Sofia Zelleroth ◽  
Alfhild Grönbladh ◽  
Mathias Hallberg ◽  
Curt Pettersson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Metabolic Diseases ◽  
De Novo ◽  
High Resolution Mass Spectrometry ◽  
De Novo Lipogenesis ◽  
Anabolic Androgenic Steroids ◽  
Lipid Profiling ◽  
Testosterone Undecanoate ◽  
Androgenic Steroids

Abstract Introduction The abuse of anabolic androgenic steroids (AASs) is a source of public concern because of their adverse effects. Supratherapeutic doses of AASs are known to be hepatotoxic and regulate the lipoproteins in plasma by modifying the metabolism of lipids in the liver, which is associated with metabolic diseases. However, the effect of AASs on the profile of lipids in plasma is unknown. Objectives To describe the changes in the plasma lipidome exerted by AASs and to discuss these changes in the light of previous research about AASs and de novo lipogenesis in the liver. Methods We treated male Wistar rats with supratherapeutic doses of nandrolone decanoate and testosterone undecanoate. Subsequently, we isolated the blood plasma and performed lipidomics analysis by liquid chromatography-high resolution mass spectrometry. Results Lipid profiling revealed a decrease of sphingolipids and glycerolipids with palmitic, palmitoleic, stearic, and oleic acids. In addition, lipid profiling revealed an increase in free fatty acids and glycerophospholipids with odd-numbered chain fatty acids and/or arachidonic acid. Conclusion The lipid profile presented herein reports the imprint of AASs on the plasma lipidome, which mirrors the downregulation of de novo lipogenesis in the liver. In a broader perspective, this profile will help to understand the influence of androgens on the lipid metabolism in future studies of diseases with dysregulated lipogenesis (e.g. type 2 diabetes, fatty liver disease, and hepatocellular carcinoma).

scholarly journals Risk of diabetes associated with fatty acids in the de novo lipogenesis pathway is independent of insulin sensitivity and response: the Insulin Resistance Atherosclerosis Study (IRAS)

2019 ◽  
Vol 7 (1) ◽  
pp. e000691 ◽  
Author(s):  
Waqas Qureshi ◽  
Ingrid D Santaren ◽  
Anthony J Hanley ◽  
Steven M Watkins ◽  
Carlos Lorenzo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Palmitic Acid ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Diabetes Incidence ◽  
Incident Type ◽  
Insulin Resistance Atherosclerosis Study

ObjectiveTo examine the associations of fatty acids in the de novo lipogenesis (DNL) pathway, specifically myristic acid (14:0), palmitic acid (16:0),cis-palmitoleic acid (c16:1 n-7),cis-myristoleic acid (c14:1n5), stearic acid (18:0) andcis-oleic acid (c18:1 n-9), with 5-year risk of type 2 diabetes. We hypothesized that DNL fatty acids are associated with risk of type 2 diabetes independent of insulin sensitivity.Research design and methodsWe evaluated 719 (mean age 55.1±8.5 years, 44.2% men, 42.3% Caucasians) participants from the Insulin Resistance Atherosclerosis Study. Multivariable logistic regression models with and without adjustment of insulin sensitivity were used to assess prospective associations of DNL fatty acids with incident type 2 diabetes.ResultsType 2 diabetes incidence was 20.3% over 5 years. In multivariable regression models, palmitic, palmitoleic, myristic, myristoleic and oleic acids were associated with increased risk of type 2 diabetes (p<0.05). Palmitic acid had the strongest association (OR per standard unit of palmitic acid 1.46; 95% CI 1.23 to 1.76; p<0.001), which remained similar with addition of insulin sensitivity and acute insulin response (AIR) to the model (OR 1.36; 95% CI 1.09 to 1.70, p=0.01). Oleic and palmitoleic acids were also independently associated with incident type 2 diabetes. In multivariable models, ratios of fatty acids corresponding to stearoyl CoA desaturase-1 and Elovl6 enzymatic activity were significantly associated with risk of type 2 diabetes independent of insulin sensitivity and AIR.ConclusionsWe observed associations of DNL fatty acids with type 2 diabetes incidence independent of insulin sensitivity.

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