Effects of Short-Term Continuous Subcutaneous Insulin Infusion on Fasting Plasma Fibroblast Growth Factor-21 Levels in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

To investigate the effects of short-term continuous subcutaneous insulin infusion (CSII) on plasma fibroblast growth factor-21 (FGF-21) levels in patients with newly diagnosed type 2 diabetes mellitus (nT2DM).Sixty-eight patients with nT2DM (nT2DM group), and 52 gender-, age- and body mass index (BMI) -matched normal glucose tolerance (NGT group) controls participated in the study. 30 nT2DM patients with FBG≥14.0 mmol/L were treated with CSII for 2 weeks, and were underwent a euglycemic–hyperinsulinemic clamp pre- and post-treatment. Plasma FGF-21 concentrations were measured with a commercial ELISA kit. The relationship between plasma FGF-21 levels and metabolic parameters was also analyzed.<0.05), accompanied by a significant increase in the whole body glucose uptake (M value) and blood glucose control. The changes in plasma FGF-21 levels (ΔFGF-21) were positively associated with the amelioration of insulin resistance shown by the changes in M value.Plasma FGF-21 level is associated with whole body insulin sensitivity and significantly reduced following short-term CSII treatment

Upper atmospheres and ionospheres of planets and satellites

The upper atmospheres of the planets and their satellites are more directly exposed to sunlight and solar wind particles than the surface or the deeper atmospheric layers. At the altitudes where the associated energy is deposited, the atmospheres may become ionized and are referred to as ionospheres. The details of the photon and particle interactions with the upper atmosphere depend strongly on whether the object has anintrinsic magnetic field that may channel the precipitating particles into the atmosphere or drive the atmospheric gas out to space. Important implications of these interactions include atmospheric loss over diverse timescales, photochemistry and the formation of aerosols, which affect the evolution, composition and remote sensing of the planets (satellites). The upper atmosphere connects the planet (satellite) bulk composition to the near-planet (-satellite) environment. Understanding the relevant physics and chemistry provides insight to the past and future conditions of these objects, which is critical for understanding their evolution. This chapter introduces the basic concepts of upper atmospheres and ionospheres in our solar system, and discusses aspects of their neutral and ion composition, wind dynamics and energy budget. This knowledge is key to putting in context the observations of upper atmospheres and haze on exoplanets, and to devise a theory that explains exoplanet demographics.Comment: Invited Revie

Klotho coreceptors inhibit signaling by paracrine fibroblast growth factor 8 subfamily ligands.

It has been recently established that Klotho coreceptors associate with fibroblast growth factor (FGF) receptor tyrosine kinases (FGFRs) to enable signaling by endocrine-acting FGFs. However, the molecular interactions leading to FGF-FGFR-Klotho ternary complex formation remain incompletely understood. Here, we show that in contrast to αKlotho, βKlotho binds its cognate endocrine FGF ligand (FGF19 or FGF21) and FGFR independently through two distinct binding sites. FGF19 and FGF21 use their respective C-terminal tails to bind to a common binding site on βKlotho. Importantly, we also show that Klotho coreceptors engage a conserved hydrophobic groove in the immunoglobulin-like domain III (D3) of the "c" splice isoform of FGFR. Intriguingly, this hydrophobic groove is also used by ligands of the paracrine-acting FGF8 subfamily for receptor binding. Based on this binding site overlap, we conclude that while Klotho coreceptors enhance binding affinity of FGFR for endocrine FGFs, they actively suppress binding of FGF8 subfamily ligands to FGFR

Atmosphere-land surface interactions and their influence on extreme rainfall and potential abrupt climate change over southern Africa

In a changing climate, changes in rainfall variability and, in particular, extreme rainfall events are likely to be highly significant for environmentally vulnerable regions such as southern Africa. It is generally accepted that sea-surface temperatures play an important role in modulating rainfall variability, thus the majority work to date has focused on these mechanisms. However past research suggests that land surface processes are also critical for rainfall variability. In particular, work has suggested that the atmosphere-land surface feedback has been important for past abrupt climate changes, such as those which occurred over the Sahara during the mid-Holocene or, more recently, the prolonged Sahelian drought. Therefore the primary aim of this work is to undertake idealised experiments using both a regional and global climate model, to test the sensitivity of rainfall variability to land surface changes over a location where such abrupt climate changes are projected to occur in the future, namely southern Africa. In one experiment, the desert conditions currently observed over southwestern Africa were extended to cover the entire subcontinent. This is based on past research which suggests a remobilisation of sand dune activity and spatial extent under various scenarios of future anthropogenic global warming. In the second experiment, savanna conditions were imposed over all of southern Africa, representing an increase in vegetation for most areas except the equatorial regions. The results suggest that a decrease in rainfall occurs in the desert run, up to 27% of total rainfall in the regional model (relative to the control), due to a reduction in available moisture, less evaporation, less vertical uplift and therefore higher near surface pressure. This result is consistent across both the regional and global model experiments. Conversely an increase in rainfall occurs in the savanna run, because of an increase in available moisture giving an increase in latent heat and therefore surface temperature, increasing vertical uplift and lowering near surface pressure. These experiments, however, are only preliminary, and form the first stage of a wider study into how the atmosphere-land surface feedback influences rainfall extremes over southern Africa in the past (when surface i.e. vegetation conditions were very different) and in the future under various scenarios of future climate change. Future work will examine how other climate models simulate the atmosphere-land surface feedback, using more realistic vegetation types based on past and future surface conditions