All biomolecules operate and interact in aqueous solutions, surrounded by a characteristic hydration shell. Virtually any conformational change of a biomolecule, e.g. the formation of a protein-protein complex or the binding of a small molecule, results in a change of the individual hydration shell.

A German company called NanoTemper Technologies has found a way to easily monitor these specific changes in the hydration shell and to derive quantitative information on interactions, conformational changes and macromolecular stability. The beauty of the concept termed Microscale Thermophoresis (MST) lies in its ability to observe and measure various parameters, such as affinities and binding energetics, at conditions which almost fully mirror the native environment of the biomolecules found in cells.

This is of great value, in particular for interactions that are difficult to access with standard methods, like the binding of small molecules or single ions to larger components of the cell, or the interactions of peptides and proteins to membrane receptors, the most important pharmaceutical drug targets.  » Read more...

Patients suffering from the autoimmune disease systemic lupus erythematosus (SLE) develop autoantibodies to chromatin and often to neutrophil proteins as well. As immune complexes of these antibodies can be deposited in kidneys, they contribute to the frequent and dangerous organ manifestation of lupus nephritis.

Recent studies suggest that neutrophil extracellular traps (NETs) might act as a source of autoantigens. NETs consist of chromatin as well as granule proteins and play an important role in immune defense after their release from neutrophils to sites of infection. Degradation of NETs is mainly promoted by DNase1 digestion which is impaired in a subset of SLE patients. A strong correlation between NET degradation status and lupus nephritis, e.g. glomerulonephritis, has been shown and therefore offers a new diagnostic method for detecting an increased risk of SLE patients to develop renal manifestations.

Based on these observations, scientists of the German Max Planck Society (MPG) have developed a technology for the assessment of an increased risk in SLE patients for developing renal manifestations – a finding that is not achieved by determination of anti-dsDNA antibody titers.  » Read more...

A few days of fasting may delay tumor progression and improve chemotherapy, a new study in mice reports. The findings indicate that fasting prior to chemotherapy treatment protects animals – and possibly humans – against the side effects of treatment. Here, Valter Longo and colleagues show in mice that fasting for 2 days in the absence of other treatments can delay the progression of different types of cancer, and may in some cases be just as effective as toxic chemotherapy drugs. However, the combination of fasting and chemotherapy appears to be more effective at making normal cells stronger (more able to resist damage from chemotherapeutic drugs) than either alone. In fact, combined fasting and chemotherapy promoted long-term, cancer-free survival in up to 40 percent of mice with neuroblastomas. Although clinical trials testing the effect of fasting in cancer treatment are still in early stages, these studies suggest that fasting cycles have the potential to boost the efficacy of chemotherapy. The results are particularly relevant for advanced-stage patients for whom standard treatment is ineffective.

The research is published in this week’s Science Translational Medicine (Sci. Transl. Med. DOI: 10.1126/scitranslmed.3003293)

An FDA-approved drug called bexarotene counters many of the effects of Alzheimer’s disease in mouse models, researchers report. The build-up of protein fragments called amyloid-beta is a key feature of the disease; everyone’s brain produces amyloid-beta, but in healthy individuals, enzymes break the fragments down, with help from a protein called ApoE. Paige Cramer and colleagues knew that bexarotene activates a protein that helps switch on the ApoEgene, and they hypothesized that the drug might therefore enhance the clearance of amyloid-beta in the brain. They gave the drug to mice engineered to have an Alzheimer’s-like condition and observed that levels of the protein fragments in the mice’s brains dropped substantially within just a few days. The mice also showed improvements in their cognitive, social and olfactory performance. Bexarotene, also known as Targretin, is currently used to treat a form of skin cancer and has a favorable safety profile, the authors note. The drug activates the nuclear receptor protein known as RXR, which binds one of two other nuclear receptors, PPAR and LXR. These receptor pairs then activate the transcription of the ApoE gene.

The research is published online by the journal Science at this week’s Science Express website.  » Read more...

Everybody knows of instances in their own life where initial “mistakes” or wrong decisions turned out to be exactly the right thing. Trivial examples include going to a party that you never really wanted to attend and ending up meeting the person of your life – or running ten minutes late and thereby avoiding a fatal car crash that had just occured down the road.

But what about the most carefully managed area in life – your own career and business? Thinking that wrong business decisions must mean the end of your career? The opposite may be the case, says Paul J.H. Schoemaker, research director of Wharton’s Mack Center for Technological Innovation and chairman and founder of consulting firm Decision Strategies International.

In his book Brilliant Mistakes: Finding Success on the Far Side of Failure, Schoemaker argues that mistakes often open the door to totally new perspectives and findings – and help you reinvent your business or personal career for good. Mistakes have been the basis for many innovations that revolutionized the way we live today – including the discovery of penicillin and the development of ATM machines.  » Read more...