Tuning liver pyruvate kinase activity up or down with a new class of allosteric modulators.

The liver isoform of pyruvate kinase (PKL) has gained interest due to its potential capacity to regulate fatty acid synthesis involved in the progression of non-alcoholic fatty liver disease (NAFLD). Here we describe a novel series of PKL modulators that can either activate or inhibit the enzyme allosterically, from a cryptic site at the interface of two protomers in the tetrameric enzyme. Starting from urolithin D, we designed and synthesised 42 new compounds.

Serendipitous Identification of a Covalent Activator of Liver Pyruvate Kinase.

Enzymes are effective biological catalysts that accelerate almost all metabolic reactions in living organisms. Synthetic modulators of enzymes are useful tools for the study of enzymatic reactions and can provide starting points for the design of new drugs. Here, we report on the discovery of a class of biologically active compounds that covalently modifies lysine residues in human liver pyruvate kinase (PKL), leading to allosteric activation of the enzyme (EC =0.

Azulene Functionalization by Iron-Mediated Addition to a Cyclohexadiene Scaffold.

The functionalization of azulenes via reaction with cationic η-iron carbonyl diene complexes under mild reaction conditions is demonstrated. A range of azulenes, including derivatives of naturally occurring guaiazulene, were investigated in reactions with three electrophilic iron complexes of varying electronic properties, affording the desired coupling products in 43-98% yield. The products were examined with UV-vis/fluorescence spectroscopy and showed interesting halochromic properties.

Pump absorption, laser amplification, and effective length in double-clad ytterbium-doped fibers with small area ratio.

We use numerical simulations with the beam propagation method (BPM) and rate equations to investigate the pump absorption and amplification characteristics in double-clad ytterbium-doped fibers with small cladding-to-core area ratios, in the range 1-3. The presence of modes with low overlap with the doped region (or alternatively, skew rays) hampers the pump absorption in a circular geometry, but we find that the effect is small for area ratios of ∼2.5 or less.

The tree species matters: Biodiversity and ecosystem service implications of replacing Scots pine production stands with Norway spruce.

The choice of tree species used in production forests matters for biodiversity and ecosystem services. In Sweden, damage to young production forests by large browsing herbivores is helping to drive a development where sites traditionally regenerated with Scots pine (Pinus sylvestris) are instead being regenerated with Norway spruce (Picea abies). We provide a condensed synthesis of the available evidence regarding the likely resultant implications for forest biodiversity and ecosystem services from this change in tree species.

Facial reconstruction of an 11-year-old female resident of 430 BC Athens.

Although modern standards of ideal proportions and facial esthetics are based mostly on observations of human faces as depicted in Classical Greek masterpieces of art, the real faces of ordinary ancient Greeks have, until now, remained elusive and subject to the imagination. Objective forensic techniques of facial reconstruction have never been applied before, because human skeletal material from Classical Greece has been extremely scarce, since most decent burials of that time required cremation. Here, the authors show stage by stage the facial reconstruction of an 11-year-old girl whose skull was unearthed in excellent condition from a mass grave with victims of the Plague that struck Athens of 430 bc.