13 research outputs found
Impact of Information Technology on the Therapy of Type-1 Diabetes: A Case Study of Children and Adolescents in Germany
Being able to manage and adjust insulin doses is a key part of managing type-1 diabetes. Children and adolescents with type-1 diabetes mellitus often have serious difficulties with this dosage adjustment. Therefore, this paper aims to investigate the impact of using novel mobile, web and communication technologies in assisting their therapy and treatment. A trial was conducted in the north-eastern part of Germany to evaluate the impact of the âMobil Diabâ, a mobile diabetes management system, on the clinical outcome. 68 subjects aged between 8 and 18 years, divided randomly into control and intervention groups, were included into the study. Metrics such as changes in the quality of metabolic control, changes in psychological parameters, usability and acceptance of the technology were used for evaluation purpose. Metabolic control was mainly assessed by the mean HbAlc. Analysis showed a good acceptance of the proposed system. An overall improvement in mean levels of HbA1c was observed, however further studies will be conducted to prove evidence of the weight and BMI improvements. Moreover, initial indications of positive impact on the improvement in psychological parameters were presumed based on the result of the conducted study. The system appeared to be an efficient and time saving tool in diabetes management
IronâSulfur Cluster Binding by Mitochondrial Monothiol Glutaredoxin-1 ofTrypanosoma brucei: Molecular Basis of IronâSulfur Cluster Coordination and Relevance for Parasite Infectivity
AIMS:
Monothiol glutaredoxins (1-C-Grxs) are small proteins linked to the cellular iron and redox metabolism. Trypanosoma brucei brucei, model organism for human African trypanosomiasis, expresses three 1-C-Grxs. 1-C-Grx1 is a highly abundant mitochondrial protein capable to bind an iron-sulfur cluster (ISC) in vitro using glutathione (GSH) as cofactor. We here report on the functional and structural analysis of 1-C-Grx1 in relation to its ISC-binding properties.
RESULTS:
An N-terminal extension unique to 1-C-Grx1 from trypanosomatids affects the oligomeric structure and the ISC-binding capacity of the protein. The active-site Cys104 is essential for ISC binding, and the parasite-specific glutathionylspermidine and trypanothione can replace GSH as the ligands of the ISC. Interestingly, trypanothione forms stable protein-free ISC species that in vitro are incorporated into the dithiol T. brucei 2-C-Grx1, but not 1-C-Grx1. Overexpression of the C104S mutant of 1-C-Grx1 impairs disease progression in a mouse model. The structure of the Grx-domain of 1-C-Grx1 was solved by nuclear magnetic resonance spectroscopy. Despite the fact that several residues--which in other 1-C-Grxs are involved in the noncovalent binding of GSH--are conserved, different physicochemical approaches did not reveal any specific interaction between 1-C-Grx1 and free thiol ligands.
INNOVATION:
Parasite Grxs are able to coordinate an ISC formed with trypanothione, suggesting a new mechanism of ISC binding and a novel function for the parasite-specific dithiol. The first 3D structure and in vivo relevance of a 1-C-Grx from a pathogenic protozoan are reported.
CONCLUSION:
T. brucei 1-C-Grx1 is indispensable for mammalian parasitism and utilizes a new mechanism for ISC binding
Geophysical Student Field Trip Baltic Sea, Cruise No. AL579, 20.08.2022 â 28.08.2022, Kiel (Germany) â Kiel (Germany), GĂ Uni Kiel
Research cruise AL579 is part of the bachelor course "Physics of the Earth System - Geophysics,
Meteorology and Oceanography" at the University of Kiel. It is the field exercise for marine
geophysics and hydroacoustics. The aim of the annually recurring cruise is to give students a
practical insight into the acquisition, processing, documentation, and interpretation of marine
geophysical data. AL579 took place from August 20th -28th 2022 with the main study areas in
Eckernförde Bay and the Bay of Mecklenburg. Parts of the scientific crew changed during a
stopover in Kiel on Wednesday, 24.8.2022. In Eckernförde Bay we mainly collected Multibeam
Echosounder (MBES) and INNOMAR Subbottom Echosounder (SES) data calibrated by CTD
measurements close to the pockmark field off Mittelgrund. On Wednesday, 24.8.2022 we tested a
new Ocean Bottom Seismometer (OBS) prototype. In the Bay of Mecklenburg, the focus was on
BlinkerhĂŒgel and the seafloor structures further west where an enigmatic stone structure was
discovered in 2021. This area was surveyed with Sidescan Sonar, MBES, SES, and CTD
measurements and several video transects with an underwater drone. We also collected two sets
of multi-channel seismic data to investigate the deeper structures of the Western Baltic Sea and
the Bay of Mecklenburg
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A Novel Way to Measure and Predict Development: A Heuristic Approach to Facilitate the Early Detection of Neurodevelopmental Disorders.
Purpose of reviewSubstantial research exists focusing on the various aspects and domains of early human development. However, there is a clear blind spot in early postnatal development when dealing with neurodevelopmental disorders, especially those that manifest themselves clinically only in late infancy or even in childhood.Recent findingsThis early developmental period may represent an important timeframe to study these disorders but has historically received far less research attention. We believe that only a comprehensive interdisciplinary approach will enable us to detect and delineate specific parameters for specific neurodevelopmental disorders at a very early age to improve early detection/diagnosis, enable prospective studies and eventually facilitate randomised trials of early intervention. In this article, we propose a dynamic framework for characterising neurofunctional biomarkers associated with specific disorders in the development of infants and children. We have named this automated detection 'Fingerprint Model', suggesting one possible approach to accurately and early identify neurodevelopmental disorders
The Dithiol Glutaredoxins of African Trypanosomes Have Distinct Roles and Are Closely Linked to the Unique Trypanothione Metabolism*
Trypanosoma brucei, the causative agent of African sleeping sickness, possesses two dithiol glutaredoxins (Grx1 and Grx2). Grx1 occurs in the cytosol and catalyzes protein deglutathionylations with kcat/Km-values of up to 2 Ă 105 mâ1 sâ1. It accelerates the reduction of ribonucleotide reductase by trypanothione although less efficiently than the parasite tryparedoxin and has low insulin disulfide reductase activity. Despite its classical CPYC active site, Grx1 forms dimeric iron-sulfur complexes with GSH, glutathionylspermidine, or trypanothione as non-protein ligands. Thus, contrary to the generally accepted assumption, replacement of the Pro is not a prerequisite for cluster formation. T. brucei Grx2 shows an unusual CQFC active site, and orthologues occur exclusively in trypanosomatids. Grx2 is enriched in mitoplasts, and fractionated digitonin lysis resulted in a co-elution with cytochrome c, suggesting localization in the mitochondrial intermembrane space. Grx2 catalyzes the reduction of insulin disulfide but not of ribonucleotide reductase and exerts deglutathionylation activity 10-fold lower than that of Grx1. RNA interference against Grx2 caused a growth retardation of procyclic cells consistent with an essential role. Grx1 and Grx2 are constitutively expressed with cellular concentrations of about 2 ÎŒm and 200 nm, respectively, in both the mammalian bloodstream and insect procyclic forms. Trypanothione reduces the disulfide form of both proteins with apparent rate constants that are 3 orders of magnitude higher than those with glutathione. Grx1 and, less efficiently, also Grx2 catalyze the reduction of GSSG by trypanothione. Thus, the Grxs play exclusive roles in the trypanothione-based thiol redox metabolism of African trypanosomes