Onset of Asian desertification by 22 Myr ago inferred from loess deposits in China

The initial desertification in the Asian interior is thought to be one of the most prominent climate changes in the Northern Hemisphere during the Cenozoic era. But the dating of this transition is uncertain, partly because desert sediments are usually scattered, discontinuous and difficult to date. Here we report nearly continuous aeolian deposits covering the interval from 22 to 6.2 million years ago, on the basis of palaeomagnetic measurements and fossil evidence. A total of 231 visually definable aeolian layers occur as brownish loesses interbedded with reddish soils. This new evidence indicates that large source areas of aeolian dust and energetic winter monsoon winds to transport the material must have existed in the interior of Asia by the early Miocene epoch, at least 14 million years earlier than previously thought. Regional tectonic changes and ongoing global cooling are probable causes of these changes in aridity and circulation in Asia.     

Structure and dynamics of the M3 muscarinic acetylcholine receptor

Acetylcholine, the first neurotransmitter to be identified, exerts many of its physiological actions via activation of a family of G-protein-coupled receptors (GPCRs) known as muscarinic acetylcholine receptors (mAChRs). Although the five mAChR subtypes (M1-M5) share a high degree of sequence homology, they show pronounced differences in G-protein coupling preference and the physiological responses they mediate. Unfortunately, despite decades of effort, no therapeutic agents endowed with clear mAChR subtype selectivity have been developed to exploit these differences. We describe here the structure of the G(q/11)-coupled M3 mAChR ('M3 receptor', from rat) bound to the bronchodilator drug tiotropium and identify the binding mode for this clinically important drug. This structure, together with that of the G(i/o)-coupled M2 receptor, offers possibilities for the design of mAChR subtype-selective ligands. Importantly, the M3 receptor structure allows a structural comparison between two members of a mammalian GPCR subfamily displaying different G-protein coupling selectivities. Furthermore, molecular dynamics simulations suggest that tiotropium binds transiently to an allosteric site en route to the binding pocket of both receptors. These simulations offer a structural view of an allosteric binding mode for an orthosteric GPCR ligand and provide additional opportunities for the design of ligands with different affinities or binding kinetics for different mAChR subtypes. Our findings not only offer insights into the structure and function of one of the most important GPCR families, but may also facilitate the design of improved therapeutics targeting these critical receptors.     

Structure of the δ-opioid receptor bound to naltrindole

The opioid receptor family comprises three members, the μ-, δ- and κ-opioid receptors, which respond to classical opioid alkaloids such as morphine and heroin as well as to endogenous peptide ligands like endorphins. They belong to the G-protein-coupled receptor (GPCR) superfamily, and are excellent therapeutic targets for pain control. The δ-opioid receptor (δ-OR) has a role in analgesia, as well as in other neurological functions that remain poorly understood. The structures of the μ-OR and κ-OR have recently been solved. Here we report the crystal structure of the mouse δ-OR, bound to the subtype-selective antagonist naltrindole. Together with the structures of the μ-OR and κ-OR, the δ-OR structure provides insights into conserved elements of opioid ligand recognition while also revealing structural features associated with ligand-subtype selectivity. The binding pocket of opioid receptors can be divided into two distinct regions. Whereas the lower part of this pocket is highly conserved among opioid receptors, the upper part contains divergent residues that confer subtype selectivity. This provides a structural explanation and validation for the 'message-address' model of opioid receptor pharmacology, in which distinct 'message' (efficacy) and 'address' (selectivity) determinants are contained within a single ligand. Comparison of the address region of the δ-OR with other GPCRs reveals that this structural organization may be a more general phenomenon, extending to other GPCR families as well.     

Cobalt doped ZrO2 decorated multiwalled carbon nanotube: A promising nanocatalyst for photodegradation of indigo carmine and eosin Y dyes

This paper reports the degradation of indigo carmine and eosin Y dyes in water, catalyzed by cobalt and multiwalled carbon nanotube modified zirconium oxide nanocomposite(Co-ZrO_2-MWCNTs) under simulated visible light. The bare ZrO_2,ZrO_2-MWCNTs, Co-ZrO_2 and Co-ZrO_2-MWCNTs with different percentage compositions of cobalt were synthesized by homogeneous co-precipitation method. Characterization of the prepared nanocomposites was carried out using X-Ray powder Diffraction(XRD), Fourier Transformer Infrared(FTIR) Spectroscopy, Transmission Electron Microscopy(TEM), Raman Spectroscopy,(UV–Vis)-Spectroscopy and Energy Dispersive Spectroscopy(EDS) for their structure, formation,morphology, size and elemental analysis. The experimental results indicated that all the cobalt and MWCNTs modified nanocomposites demonstrated higher photocatalytic activities compared to the bare ZrO_2. The most efficient catalyst(0.5% Co-ZrO_2-MWCNTs) with the band gap and Ka values of 5.21 e V and 16.86*10~(-3) min~(-1) respectively exhibited 98% degradation efficiency toward indigo carmine and 87% toward eosin Y in 180 min.     

Early Pliocene hominids from Gona, Ethiopia

Comparative biomolecular studies suggest that the last common ancestor of humans and chimpanzees, our closest living relatives, lived during the Late Miocene-Early Pliocene. Fossil evidence of Late Miocene-Early Pliocene hominid evolution is rare and limited to a few sites in Ethiopia, Kenya and Chad. Here we report new Early Pliocene hominid discoveries and their palaeoenvironmental context from the fossiliferous deposits of As Duma, Gona Western Margin (GWM), Afar, Ethiopia. The hominid dental anatomy (occlusal enamel thickness, absolute and relative size of the first and second lower molar crowns, and premolar crown and radicular anatomy) indicates attribution to Ardipithecus ramidus. The combined radioisotopic and palaeomagnetic data suggest an age of between 4.51 and 4.32 million years for the hominid finds at As Duma. Diverse sources of data (sedimentology, faunal composition, ecomorphological variables and stable carbon isotopic evidence from the palaeosols and fossil tooth enamel) indicate that the Early Pliocene As Duma sediments sample a moderate rainfall woodland and woodland/grassland.     

Evolutionary genetics: CCR5 mutation and plague protection

A recent and prevalent mutation in the chemokine receptor CCR5 in humans of northern European ancestry has been proposed to provide protection against bubonic plague. Here we infect both normal and CCR5-deficient mice with the bacterium Yersinia pestis, the cause of the plague epidemics that wiped out one-third of Europeans in the Middle Ages, and find no difference in either bacterial growth or survival time between the two groups. Unless the pathogenesis of Yersinia infection differs markedly between mice and humans, our results indicate that CCR5 deficiency in people is unlikely to protect against plague.     

Biologically inspired oxidation catalysis

The development of processes for selective hydrocarbon oxidation is a goal that has long been pursued. An additional challenge is to make such processes environmentally friendly, for example by using non-toxic reagents and energy-efficient catalytic methods. Excellent examples are naturally occurring iron- or copper-containing metalloenzymes, and extensive studies have revealed the key chemical principles that underlie their efficacy as catalysts for aerobic oxidations. Important inroads have been made in applying this knowledge to the development of synthetic catalysts that model enzyme function. Such biologically inspired hydrocarbon oxidation catalysts hold great promise for wide-ranging synthetic applications.     

Functional asymmetry in Caenorhabditis elegans taste neurons and its computational role in chemotaxis

Chemotaxis in Caenorhabditis elegans, like chemotaxis in bacteria, involves a random walk biased by the time derivative of attractant concentration, but how the derivative is computed is unknown. Laser ablations have shown that the strongest deficits in chemotaxis to salts are obtained when the ASE chemosensory neurons (ASEL and ASER) are ablated, indicating that this pair has a dominant role. Although these neurons are left-right homologues anatomically, they exhibit marked asymmetries in gene expression and ion preference. Here, using optical recordings of calcium concentration in ASE neurons in intact animals, we demonstrate an additional asymmetry: ASEL is an ON-cell, stimulated by increases in NaCl concentration, whereas ASER is an OFF-cell, stimulated by decreases in NaCl concentration. Both responses are reliable yet transient, indicating that ASE neurons report changes in concentration rather than absolute levels. Recordings from synaptic and sensory transduction mutants show that the ON-OFF asymmetry is the result of intrinsic differences between ASE neurons. Unilateral activation experiments indicate that the asymmetry extends to the level of behavioural output: ASEL lengthens bouts of forward locomotion (runs) whereas ASER promotes direction changes (turns). Notably, the input and output asymmetries of ASE neurons are precisely those of a simple yet novel neuronal motif for computing the time derivative of chemosensory information, which is the fundamental computation of C. elegans chemotaxis. Evidence for ON and OFF cells in other chemosensory networks suggests that this motif may be common in animals that navigate by taste and smell.