A supernova origin for dust in a high-redshift quasar

Interstellar dust plays a crucial role in the evolution of the Universe by assisting the formation of molecules, by triggering the formation of the first low-mass stars, and by absorbing stellar ultraviolet-optical light and subsequently re-emitting it at infrared/millimetre wavelengths. Dust is thought to be produced predominantly in the envelopes of evolved (age >1 Gyr), low-mass stars. This picture has, however, recently been brought into question by the discovery of large masses of dust in the host galaxies of quasars at redshift z > 6, when the age of the Universe was less than 1 Gyr. Theoretical studies, corroborated by observations of nearby supernova remnants, have suggested that supernovae provide a fast and efficient dust formation environment in the early Universe. Here we report infrared observations of a quasar at redshift 6.2, which are used to obtain directly its dust extinction curve. We then show that such a curve is in excellent agreement with supernova dust models. This result demonstrates a supernova origin for dust in this high-redshift quasar, from which we infer that most of the dust at high redshifts probably has the same origin.     

Whisker movements evoked by stimulation of single pyramidal cells in rat motor cortex

Neuronal activity in the motor cortex is understood to be correlated with movements, but the impact of action potentials (APs) in single cortical neurons on the generation of movement has not been fully determined. Here we show that trains of APs in single pyramidal cells of rat motor cortex can evoke long sequences of small whisker movements. For layer-5 pyramids, we find that evoked rhythmic movements have a constant phase relative to the AP train, indicating that single layer-5 pyramids can reset the rhythm of whisker movements. Action potentials evoked in layer-6 pyramids can generate bursts of rhythmic whisking, with a variable phase of movements relative to the AP train. An increasing number of APs decreases the latency to onset of movement, whereas AP frequency determines movement direction and amplitude. We find that the efficacy of cortical APs in evoking whisker movements is not dependent on background cortical activity and is greatly enhanced in waking rats. We conclude that in vibrissae motor cortex sparse AP activity can evoke movements.     

Subatomic and atomic crystallographic studies of aldose reductase: implications for inhibitor binding

The determination of several of aldose reductase-inhibitor complexes at subatomic resolution has revealed new structural details, including the specific interatomic contacts involved in inhibitor binding. In this article, we review the structures of the complexes of ALR2 with IDD 594 (resolution: 0.66 Å, IC50 (concentration of the inhibitor that produced half-maximal effect): 30 nM, space group: P2¹), IDD 393 (resolution: 0.90 Å, IC50: 6 nM, space group: P1), fidarestat (resolution: 0.92 Å, IC50: 9 nM, space group: P2¹) and minalrestat (resolution: 1.10 Å, IC50: 73 nM, space group: P1). The structures are compared and found to be highly reproductible within the same space group (root mean square (RMS) deviations: 0.15 0.3 Å). The mode of binding of the carboxylate inhibitors IDD 594 and IDD 393 is analysed. The binding of the carboxylate head can be accurately determined by the subatomic resolution structures, since both the protonation states and the positions of the atoms are very precisely known. The differences appear in the binding in the specificity pocket. The high-resolution structures explain the differences in IC50, which are confirmed both experimentally by mass spectrometry measures of VC50 and theoretically by free energy perturbation calculations. The binding of the cyclic imide inhibitors fidarestat and minalrestat is also described, focusing on the observation of a Cl^- ion which binds simultaneously with fidarestat. The presence of this anion, binding also to the active site residue His110, leads to a mechanism in which the inhibitor can bind in a neutral state and then become charged inside the active site pocket. This mechanism can explain the excellent in vivo properties of cyclic imide inhibitors. In summary, the complete and detailed information supplied by the subatomic resolution structures can explain the differences in binding energy of the different inhibitors.     

Vigorous exchange between the Indian and Atlantic oceans at the end of the past five glacial periods

The magnitude of heat and salt transfer between the Indian and Atlantic oceans through 'Agulhas leakage' is considered important for balancing the global thermohaline circulation. Increases or reductions of this leakage lead to strengthening or weakening of the Atlantic meridional overturning and associated variation of North Atlantic Deep Water formation. Here we show that modern Agulhas waters, which migrate into the south Atlantic Ocean in the form of an Agulhas ring, contain a characteristic assemblage of planktic foraminifera. We use this assemblage as a modern analogue to investigate the Agulhas leakage history over the past 550,000 years from a sediment record in the Cape basin. Our reconstruction indicates that Indian-Atlantic water exchange was highly variable: enhanced during present and past interglacials and largely reduced during glacial intervals. Coherent variability of Agulhas leakage with northern summer insolation suggests a teleconnection to the monsoon system. The onset of increased Agulhas leakage during late glacial conditions took place when glacial ice volume was maximal, suggesting a crucial role for Agulhas leakage in glacial terminations, timing of interhemispheric climate change and the resulting resumption of the Atlantic meridional overturning circulation.     

Calcium transients and intramembrane charge movement in skeletal muscle fibres

Myoplasmic calcium transients in response to pulse depolarisations have been monitored using the dye antipyralazo III, which provides a linear measure of the change in cytoplasmic free calcium concentration. Intramembrane charge movements were recorded simultaneously with the calcium transients. Except for its initial phase, the calcium transient during each pulse closely followed the time course expected for calcium redistribution between three intracellular compartments with time-independent flux coefficients. The time at which the flux coefficients attained their steady values occurred just after the intramembrane charge movement had been completed. This is the required sequence if charge movement were to control one or more coefficients f or calcium fluxes across the sarcoplasmic reliculum membrane.     

The first mite: insect genealogy in Hooke’s Micrographia*

What happens when you take the idea of the biblical Adam—the first human – and apply it to insects? You create an origin story for Nature’s tiniest creatures, one that gives them ‘a Pedigree as ancient as the first creation’. This the naturalist Robert Hooke argued in his treatise, the Micrographia (1665). In what follows, I will retrace how Hooke endeavoured to show that insects—then widely believed to have arisen out of the dirt – were the products of an ancient lineage. These genealogies, while constructed from empirical observation, were conjectures of the imagination. Section 2 shows how Hooke introduced the concept of a ‘prime parent’ (an Adam-insect) to explain the anatomical similarities between ‘mites’. Section 3 demonstrates how Hooke defined the family of “gnats” as tiny machines built from the same components and relates Hookean genealogies to contemporary ideas about Noah’s Ark. Section 4 shows how Hooke outlined the morphology of ‘insects’ (delineating what we now call arthropods). Section 5 explores how Hooke used fossils to study these animals in the distant past. In sum, Hooke was turning natural history – collecting and describing insects – into natural history: reconstructing their origins.     

Molecular mechanisms of centrosome and cytoskeleton anchorage at the nuclear envelope

Cell polarization is a fundamental process underpinning organismal development, and tissue homeostasis, which requires an orchestrated interplay of nuclear, cytoskeletal, and centrosomal structures. The underlying molecular mechanisms, however, still remain elusive. Here we report that kinesin-1/nesprin-2/SUN-domain macromolecular assemblies, spanning the entire nuclear envelope (NE), function in cell polarization by anchoring cytoskeletal structures to the nuclear lamina. Nesprin-2 forms complexes with the kinesin-1 motor protein apparatus by associating with and recruiting kinesin light chain1 (KLC1) to the outer nuclear membrane. Similar to nesprin-2, KLC1 requires lamin A/C for proper NE localization. The depletion of nesprin-2 or KLC1, or the uncoupling of nesprin-2/SUN-domain protein associations impairs cell polarization during wounding and dislodges the centrosome from the NE. In addition nesprin-2 loss has profound effects on KLC1 levels, the cytoskeleton, and Golgi apparatus organization. Collectively these data show that NE-associated proteins are pivotal determinants of cell architecture and polarization.     

Large-scale production of functional membrane proteins

The preparation of sufficient amounts of high-quality samples is still the major bottleneck for the characterization of membrane proteins by in vitro approaches. The hydrophobic nature, the requirement for complicated transport and modification pathways, and the often observed negative effects on membrane properties are intrinsic features of membrane proteins that frequently cause significant problems in overexpression studies. Establishing efficient protocols for the production of functionally folded membrane proteins is therefore a challenging task, and numerous specific characteristics have to be considered. In addition, a variety of expression systems have been developed, and choice of appropriate techniques could strongly depend on the desired target membrane proteins as well as on their intended applications. The production of membrane proteins is a highly dynamic field and new or modified approaches are frequently emerging. The review will give an overview of currently established processes for the production of functionally folded membrane proteins.     

Regionale Inkorporation der optischen Isomeren der Aminosäure Prolin-H3 im Autoradiogramm des Mäusegehirns

Summary Comparative labelling of the mouse brain with tritiatedd, l-proline andl-proline reveals a dissimilarity of incorporation between the optical isomers of this amino acid. The differential regional distribution pattern ofd-proline can be correlated to the cerebral distribution of the enzyme activity ofd-aminoacid-oxidase in the mouse brain.

---

---

Die Arbeit wurde mit Mitteln des Bundesministers für wissenschaftliche Forschung gefördert.