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Children followed in the TEDDY study are diagnosed with type 1 diabetes at an early stage of disease.

The Environmental Determinants of Diabetes in the Young (TEDDY) study is designed to identify environmental exposures triggering islet autoimmunity and type 1 diabetes (T1D) in genetically high-risk children. We describe the first 100 participants diagnosed with T1D, hypothesizing that (i) they are diagnosed at an early stage of disease, (ii) a high proportion are diagnosed by an oral glucose tole

Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown.

A central hurdle in developing small interfering RNAs (siRNAs) as therapeutics is the inefficiency of their delivery across the plasma and endosomal membranes to the cytosol, where they interact with the RNA interference machinery. With the aim of improving endosomal release, a poorly understood and inefficient process, we studied the uptake and cytosolic release of siRNAs, formulated in lipoplexe

Non-Renal Effects and the Risk Assessment of Environmental Cadmium Exposure.

Exposure to cadmium (Cd) has long been recognized as a health hazard, both in industry and in general populations with high exposure. Under the currently prevailing health risk assessment, the relationship between urinary Cd concentrations (U-Cd) and tubular proteinuria is used. However, doubts have recently been raised regarding the justification of basing the risk assessment on this relationship

Legal analysis of the EU policy for sustainable transport biofuels

The enforcement and implementation of separate aspects of sustainable development and environmental sustainability can be challenging and innovative due to the complexity of this task. Appropriate policy and legal approaches and tools can be needed for this purpose. In this article, the EU experience of developing the framework for sustainable transport biofuels and special structural elements for

The Shapes of Z-alpha(1)-Antitrypsin Polymers in Solution Support the C-Terminal Domain-Swap Mechanism of Polymerization

Emphysema and liver cirrhosis can be caused by the Z mutation (Glu342Lys) in the serine protease inhibitor alpha 1-antitrypsin (alpha 1AT), which is found in more than 4% of the Northern European population. Homozygotes experience deficiency in the lung concomitantly with a massive accumulation of polymers within hepatocytes, causing their destruction. Recently, it was proposed that Z-alpha 1AT po

Characteristics of MHC Class I Genes in House Sparrows Passer domesticus as Revealed by Long cDNA Transcripts and Amplicon Sequencing.

In birds the major histocompatibility complex (MHC) organization differs both among and within orders; chickens Gallus gallus of the order Galliformes have a simple arrangement, while many songbirds of the order Passeriformes have a more complex arrangement with larger numbers of MHC class I and II genes. Chicken MHC genes are found at two independent loci, classical MHC-B and non-classical MHC-Y,

2s photoionization and subsequent Auger cascade in atomic Si

The 2s photoionization and subsequent Auger transition cascade in atomic Si were studied by means of synchrotron-radiation-induced electron spectroscopy. After the 2s photoionization, the core hole states decay predominantly by a two-step Auger transition cascade into the triply ionized [Ne]nl states. The ionization channels of the 2s core-ionized Si+ atoms to Si3+ ions were observed by measuring

Prediction of hydration free energies for the SAMPL4 data set with the AMOEBA polarizable force field.

Hydration free energy calculations are often used to validate molecular simulation methodologies and molecular mechanics force fields. We use the free-energy perturbation method together with the AMOEBA polarizable force field and the Poltype parametrization protocol to predict the hydration free energies of 52 molecules as part of the SAMPL4 blind challenge. For comparison, similar calculations a

Superior photoprotective motifs and mechanisms in eumelanins uncovered.

Human pigmentation is a complex phenomenon commonly believed to serve a photoprotective function through the generation and strategic localization of black insoluble eumelanin biopolymers in sun exposed areas of the body. Despite compelling biomedical relevance to skin cancer and melanoma, eumelanin photoprotection is still an enigma: What makes this pigment so efficient in dissipating the excess

Emulsifying triglycerides with dairy phospholipids instead of soy lecithin modulates gut lipase activity

A high energy supply and appropriate amount of polyunsaturated fatty acids is crucial for proper growth and development in neonates. The capacity for fatty acid absorption in newborns is however hampered due to an undeveloped pancreatic function combined with a low bile output. This seems in particular to limit fatty acid absorption in babies given infant formulas. Since interaction between the li

Implementation of Molecularly Imprinted Polymer Beads for Surface Enhanced Raman Detection

Molecularly imprinted polymers (MIPs) have a predesigned molecular recognition capability that can be used to build robust chemical sensors. MIP-based chemical sensors allow label-free detection and are particularly interesting due to their simple operation. In this work we report the use of thiol-terminated MIP microspheres to construct surfaces for detection of a model organic analyte, nicotine,

Circulating Fibroblast Growth Factor-23 Is Associated With Fat Mass and Dyslipidemia in Two Independent Cohorts of Elderly Individuals

Objective-Disturbances in mineral metabolism define an increased cardiovascular risk in patients with chronic kidney disease. Fibroblast growth factor-23 (FGF23) is a circulating regulator of phosphate and vitamin D metabolism and has recently been implicated as a putative pathogenic factor in cardiovascular disease. Because other members of the FGF family play a role in lipid and glucose metaboli

Formation of short-chain Fatty acids, excretion of anthocyanins, and microbial diversity in rats fed blackcurrants, blackberries, and raspberries.

Introduction. Berries contain high amounts of dietary fibre and flavonoids and have been associated with improved metabolic health. The mechanisms are not clear but the formation of SCFAs, especially propionic and butyric acids, could be important. The potent antioxidant and antimicrobial properties of flavonoids could also be a factor, but little is known about their fate in the gastrointestinal

Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study

Patients with multiple myeloma (MM) have an increased risk of venous thrombosis. Interestingly, excess risk of venous thromboembolism has been observed among patients with monoclonal gammopathy of undetermined significance (MGUS). Using population-based data from Sweden, we assessed the risks of venous and arterial thrombosis in 18 627 MM and 5326 MGUS patients diagnosed from 1958 to 2006, compare

Antagonistic Human FcγRIIB (CD32B) Antibodies Have Anti-Tumor Activity and Overcome Resistance to Antibody Therapy In Vivo.

Therapeutic antibodies have transformed cancer therapy, unlocking mechanisms of action by engaging the immune system. Unfortunately, cures rarely occur and patients display intrinsic or acquired resistance. Here, we demonstrate the therapeutic potential of targeting human (h) FcγRIIB (CD32B), a receptor implicated in immune cell desensitization and tumor cell resistance. FcγRIIB-blocking antibodie