'Gut health': a new objective in medicine?

'Gut health' is a term increasingly used in the medical literature and by the food industry. It covers multiple positive aspects of the gastrointestinal (GI) tract, such as the effective digestion and absorption of food, the absence of GI illness, normal and stable intestinal microbiota, effective immune status and a state of well-being. From a scientific point of view, however, it is still extremely unclear exactly what gut health is, how it can be defined and how it can be measured. The GI barrier adjacent to the GI microbiota appears to be the key to understanding the complex mechanisms that maintain gut health. Any impairment of the GI barrier can increase the risk of developing infectious, inflammatory and functional GI diseases, as well as extraintestinal diseases such as immune-mediated and metabolic disorders. Less clear, however, is whether GI discomfort in general can also be related to GI barrier functions. In any case, methods of assessing, improving and maintaining gut health-related GI functions are of major interest in preventive medicine

Cytoskeletal protein kinases: titin and its relations in mechanosensing

Titin, the giant elastic ruler protein of striated muscle sarcomeres, contains a catalytic kinase domain related to a family of intrasterically regulated protein kinases. The most extensively studied member of this branch of the human kinome is the Ca2+–calmodulin (CaM)-regulated myosin light-chain kinases (MLCK). However, not all kinases of the MLCK branch are functional MLCKs, and about half lack a CaM binding site in their C-terminal autoinhibitory tail (AI). A unifying feature is their association with the cytoskeleton, mostly via actin and myosin filaments. Titin kinase, similar to its invertebrate analogue twitchin kinase and likely other “MLCKs”, is not Ca2+–calmodulin-activated. Recently, local protein unfolding of the C-terminal AI has emerged as a common mechanism in the activation of CaM kinases. Single-molecule data suggested that opening of the TK active site could also be achieved by mechanical unfolding of the AI. Mechanical modulation of catalytic activity might thus allow cytoskeletal signalling proteins to act as mechanosensors, creating feedback mechanisms between cytoskeletal tension and tension generation or cellular remodelling. Similar to other MLCK-like kinases like DRAK2 and DAPK1, TK is linked to protein turnover regulation via the autophagy/lysosomal system, suggesting the MLCK-like kinases have common functions beyond contraction regulation

Top Quark Mass Measurement in the lepton plus jets Channel Using a Matrix Element Method and in situ Jet Energy Calibration

A precision measurement of the top quark mass m(t) is obtained using a sample of t (t) over bar events from p (p) over bar collisions at the Fermilab Tevatron with the CDF II detector. Selected events require an electron or muon, large missing transverse energy, and exactly four high-energy jets, at least one of which is tagged as coming from a b quark. A likelihood is calculated using a matrix element method with quasi-Monte Carlo integration taking into account finite detector resolution and jet mass effects. The event likelihood is a function of mt and a parameter Delta(JES) used to calibrate the jet energy scale in situ. Using a total of 1087 events in 5.6 fb(-1) of integrated luminosity, a value of m(t) 173.0 +/- 1.2 GeV/c(2) is measured