scholarly journals Genetic Risk Scores for Diabetes Diagnosis and Precision Medicine

2019 ◽  
Vol 40 (6) ◽  
pp. 1500-1520 ◽  
Author(s):  
Miriam S Udler ◽  
Mark I McCarthy ◽  
Jose C Florez ◽  
Anubha Mahajan
Keyword(s):  
Risk Scores ◽  
Diabetes Diagnosis ◽  
Physiological Mechanisms ◽  
Risk Variants ◽  
Polygenic Scores ◽  
Disease Predisposition ◽  
Dna Sequence Variants

Abstract During the last decade, there have been substantial advances in the identification and characterization of DNA sequence variants associated with individual predisposition to type 1 and type 2 diabetes. As well as providing insights into the molecular, cellular, and physiological mechanisms involved in disease pathogenesis, these risk variants, when combined into a polygenic score, capture information on individual patterns of disease predisposition that have the potential to influence clinical management. In this review, we describe the various opportunities that polygenic scores provide: to predict diabetes risk, to support differential diagnosis, and to understand phenotypic and clinical heterogeneity. We also describe the challenges that will need to be overcome if this potential is to be fully realized.

scholarly journals The Landscape of microRNAs in βCell: Between Phenotype Maintenance and Protection

2021 ◽  
Vol 22 (2) ◽  
pp. 803
Author(s):  
Giuseppina Emanuela Grieco ◽  
Noemi Brusco ◽  
Giada Licata ◽  
Daniela Fignani ◽  
Caterina Formichi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Β Cell ◽  
Physiological Mechanisms ◽  
Effective Strategies ◽  
Chronic Hyperglycaemia ◽  
Shed Light

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules.

Characterization of damage and biotic factors associated with the decline of Eucalyptus wandoo in southwest Western Australia

2005 ◽  
Vol 35 (11) ◽  
pp. 2589-2602 ◽  
Author(s):  
Ryan J Hooper ◽  
K Sivasithamparam
Keyword(s):  
Western Australia ◽  
Partial Harvest ◽  
Foliage Density ◽  
Density Ratios ◽  
The Relationship ◽  
Mixed Age ◽  
Eucalyptus Wandoo

Crown decline of wandoo, Eucalyptus wandoo, in southwest Western Australia has escalated over the last 10 years, so very few unaffected stands remain. To assess the canopy-damage characteristics of trees in decline a destructive, partial-harvest method was used to sample branches in natural mixed-age stands. Necrosis of common cankers was closely associated with type-1 borer damage, characterized by "longitudinal" gallery structure on declining trees only. Cankers were found to be consistently more severe on declining trees, with decay regions affecting a greater proportion of sapwood tissue. Several infestations causing type-1 borer damage that varied in age were found on declining branches, providing evidence of cyclical damage events. Type-2 borer damage characterized by "ring-barking" gallery structure caused extensive damage in canopies, but was not always associated with decline. Interactions between foliage density and canker score showed that 17.8% and 63.1% of the variability in foliage-density ratios was accounted for in declining intermediate-health and unhealthy classes, respectively. The relationship was negligible for the healthy class (9.9%), providing strong evidence that cankers are causing foliage loss in declining canopies. Evidence suggests that an interaction between type-1 borer infestations and decay-causing fungi is responsible for the decline in E. wandoo wandoo canopies.

scholarly journals Involvement of dietitians in diabetes care, results from a secondary care hospital in Greece

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Zoe Pafili ◽  
Sophia Samara ◽  
Charilaos Dimosthenopoulos ◽  
Olga Gkortzi
Keyword(s):  
Type 2 Diabetes ◽  
Diabetes Care ◽  
Secondary Care ◽  
Diabetes Management ◽  
Nutrition Therapy ◽  
Dietary Advice ◽  
Diabetes Diagnosis ◽  
Diabetes Patients

AbstractIntroductionAccording to diabetes care standards nutrition therapy should be an integral part of diabetes management, and all individuals with diabetes should be referred to a registered dietitian for nutrition therapy at—or soon after—diagnosis and for ongoing follow-up. There is limited international data that indicate that a large percentage of people with diabetes have not received structured diabetes education and have not visited a dietitian. The aim of this study was to assess the involvement of dietitians in diabetes care in Greece.Materials and MethodsAll adult diabetic patients admitted to a secondary care general hospital in Greece during 30 consecutive days were included in the study. Patients admitted in the ICU, CICU, day clinics and hemodialysis patients were excluded. Data were obtained by personal interviews using a 40 item questionnaire which included 10 questions regarding number of visits to dietitians for diabetes management, whether patients were referred by their doctors or sought dietary advice by their own, reasons for visiting a dietitian, goal achievement and patient satisfaction.ResultsIn total 124 patients (68 males and 56 females) with diabetes were admitted to the hospital during the study period (4 type 1, 114 type 2 and 6 pregnancy diabetes). Data were obtained from 3 (22.8 ± 6 yrs, 26.1 ± 5.7kg/m2,8.3 ± 5.9 yrs with diabetes),105 (76.6 ± 11.3 yrs, 28.0 ± 5.3 kg/m2, 12.8 ± 9.3 yrs with diabetes), and 5 (32.6 ± 4.4 yrs, 28.5 ± 4.0 kg/m2) patients with type 1, type 2 and pregnancy diabetes respectively. Two out of 3 type 1 diabetes and 1 out of 5 patients with pregnancy diabetes interviewed reported to have been referred to a dietitian by their doctor. Only 5.7% (6 patients) of type 2 diabetes patients reported to have been referred to a dietitian by their doctor and another 5.7% have visited a dietitian on their own initiative. Five out of 6 referrals were at diabetes diagnosis. The number of encounters with a dietitian ranged from 1 to 24 with patients seeking to loose weight having the greater number of encounters. Of type 2 diabetes patients 94.3% did not receive lifestyle advice before commencing diabetes medication whereas 25% did not receive any dietary advice by any health professional even after starting medication.ConclusionsIn our cohort the majority of diabetes patients had not received dietary counseling by a dietitian, whereas about one fourth of type 2 diabetes patients had not received any dietary advice.

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.

The TUDID Study – Background and Design of a Prospective Cohort

2020 ◽  
Author(s):  
Benjamin Assad Jaghutriz ◽  
Robert Wagner ◽  
Stephanie Kullmann ◽  
Louise Fritsche ◽  
Sabine S. Eckstein ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Laboratory Tests ◽  
Diabetes Complications ◽  
Treatment Options ◽  
University Hospital ◽  
Tailored Treatment ◽  
The Individual

AbstractPrevalence of both type 1 and type 2 diabetes mellitus is growing worldwide and one major cause for morbidity and mortality. However, not every patient develops diabetes-related complications, but causes for the individual susceptibility are still not fully understood. As a platform to address this, we initiated the TUDID (TUebingen DIabetes Database) study, a prospective, monocentric, observational study that includes adults with diabetes mellitus who are treated in the inpatient clinic of a University Hospital in southern Germany. Besides a thorough clinical examination and extensive laboratory tests (with integrated biobanking), major study focuses are the kidneys, the eyes, the vasculature as well as cognition and mood where standardized investigations for early stages for diabetes complications are performed. Analyses of the data generated by this precise characterization of diabetes-related complications will contribute to our understanding of the development and course of such complications, and thus facilitate the implementation of tailored treatment options that can reduce the risk and severity of diabetes-related complications.

scholarly journals Characterization of cDNAs encoding isoforms of hamster 3 beta-hydroxysteroid dehydrogenase/delta 5-->4 isomerase

1998 ◽  
Vol 20 (1) ◽  
pp. 99-110 ◽  
Author(s):  
FM Rogerson ◽  
J Courtemanche ◽  
A Fleury ◽  
JG LeHoux ◽  
JI Mason ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Cdna Libraries ◽  
Sexually Dimorphic ◽  
High Affinity ◽  
Liver And Kidney ◽  
Low Levels ◽  
Type 3

Western blot analyses of various hamster tissues reveal high levels of expression of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in adrenal and liver, and moderate levels of expression in kidney. The expression in liver is sexually dimorphic; very high levels of protein are observed in adult male liver but very low levels are seen in the female liver. Three distinct cDNAs encoding isoforms of 3 beta-HSD were isolated from hamster cDNA libraries. The type 1 isoform is a high-affinity dehydrogenase/isomerase expressed in adrenal and male kidney. The type 2 isoform is also a high-affinity dehydrogenase/isomerase expressed in kidney and male liver. The type 3 enzyme is a 3-ketosteroid reductase expressed predominantly in kidney. Sequencing of the clones showed that all three are structurally very similar, although types 1 and 2 share the greatest degree of similarity. Immunohistochemical staining for 3 beta-HSD in the adrenal was found throughout the adrenal cortex. In the kidney staining was confined to tubules, and in the liver, heavy staining was found in hepatocytes. The cloning of cDNAs for 3 beta-HSD from the liver and kidney should help in elucidating the function of this enzyme in these tissues.

Prevalence and Molecular Characterization of Human T Cell Leukemia Virus Type 2 in a Group of Intravenous Drug Users Coinfected with HIV Type 1 in Portugal

2005 ◽  
Vol 21 (4) ◽  
pp. 249-255 ◽  
Author(s):  
Ana Filipa Silva ◽  
Catarina Almeida ◽  
Helena Cortes Martins ◽  
Rodrigo Coutinho ◽  
Emília Leitão ◽  
...  
Keyword(s):  
Drug Users ◽  
Leukemia Virus ◽  
Intravenous Drug Users ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Hiv Type 1

scholarly journals Systematic Functional Characterization of Candidate Causal Genes for Type 2 Diabetes Risk Variants

Diabetes ◽  
2016 ◽  
Vol 65 (12) ◽  
pp. 3805-3811 ◽  
Author(s):  
Soren K. Thomsen ◽  
Alessandro Ceroni ◽  
Martijn van de Bunt ◽  
Carla Burrows ◽  
Amy Barrett ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Functional Characterization ◽  
Diabetes Risk ◽  
Risk Variants ◽  
Causal Genes

scholarly journals Novel LinA Type 3 δ-Hexachlorocyclohexane Dehydrochlorinase

2015 ◽  
Vol 81 (21) ◽  
pp. 7553-7559 ◽  
Author(s):  
Nidhi Shrivastava ◽  
Zbynek Prokop ◽  
Ashwani Kumar
Keyword(s):  
Amino Acid ◽  
Primary Structure ◽  
Degradation Pathway ◽  
Amino Acid Residues ◽  
Hch Isomers ◽  
New Variant ◽  
Type 3

ABSTRACTLinA is the first enzyme of the microbial degradation pathway of a chlorinated insecticide, hexachlorocyclohexane (HCH), and mediates the dehydrochlorination of α-, γ-, and δ-HCH. Its two variants, LinA type 1 and LinA type 2, which differ at 10 out of 156 amino acid residues, have been described. Their activities for the metabolism of different HCH isomers differ considerably but overall are high for γ-HCH, moderate for α-HCH, low for δ-HCH, and lacking for β-HCH. Here, we describe the characterization of a new variant of this enzyme, LinA type 3, whose gene was identified from the metagenome of an HCH-contaminated soil sample. Its deduced primary structure in the region spanning amino acid residues 1 to 147 of the protein exhibits 17 and 12 differences from LinA type 1 and LinA type 2, respectively. In addition, the residues GIHFAPS, present at the region spanning residues 148 to 154 in both LinA type 1 and LinA type 2, are deleted in LinA type 3.The activity of LinA type 3 for the metabolism of δ-HCH is several orders of magnitude higher than that of LinA type 1 or LinA type 2 and can be useful for improvement of the metabolism of δ-HCH.

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