The Homo sapiens Cave hominin site of Mulan Mountain, Jiangzhou District, Chongzuo, Guangxi with emphasis on its age

One of the most hotly debated and frontal issues in paleoanthropology focuses on the origins of modern humans. Recently, an incomplete hominin mandible with a distinctly weaker mental protuberance than modern human and a great variety of coexisting fossil mammals were unearthed from the Homo sapiens Cave of Mulan Mountain, Chongzuo, Guangxi. The mammalian fauna from the Homo sapiens Cave characterized by the combination of Elephas kiangnanensis, first occurring Elephas maixmus, and Megatapirus augustus, and strikingly different from the Early Pleistocene Gigantopithecus fauna and the Middle Pleistocene Ailuropoda-Stogodon fauna of South China could be regarded as an early representive of the typical Asian elephant fauna. Faunal analysis, biostratigraphic correlation, and, most importantly, U-series dating all consistently support an estimate of ca. 110 ka for the age of the fossil Homo sapiens and coexisting mammalian fauna, that is, the early Late Pleistocene. The fauna is mainly made up of tropical-subtropical elements, but grassland elements have a much greater variety than forest elements, which probably indicates a drier climate at that time. This discovery of early Homo sapiens at the Mulan Mountain will play a significant role in the study of the origin and its environmental background of modern humans.     

Adaptation of pineal expressed teleost exo-rod opsin to non-image forming photoreception through enhanced Meta II decay

Photoreception by vertebrates enables both image-forming vision and non-image-forming responses such as circadian photoentrainment. Over the recent years, distinct non-rod non-cone photopigments have been found to support circadian photoreception in diverse species. By allowing specialization to this sensory task a selective advantage is implied, but the nature of that specialization remains elusive. We have used the presence of distinct rod opsin genes specialized to either image-forming (retinal rod opsin) or non-image-forming (pineal exo-rod opsin) photoreception in ray-finned fish (Actinopterygii) to gain a unique insight into this problem. A comparison of biochemical features for these paralogous opsins in two model teleosts, Fugu pufferfish (Takifugu rubripes) and zebrafish (Danio rerio), reveals striking differences. While spectral sensitivity is largely unaltered by specialization to the pineal environment, in other aspects exo-rod opsins exhibit a behavior that is quite distinct from the cardinal features of the rod opsin family. While they display a similar thermal stability, they show a greater than tenfold reduction in the lifetime of the signaling active Meta II photoproduct. We show that these features reflect structural changes in retinal association domains of helices 3 and 5 but, interestingly, not at either of the two residues known to define these characteristics in cone opsins. Our findings suggest that the requirements of non-image-forming photoreception have lead exo-rod opsin to adopt a characteristic that seemingly favors efficient bleach recovery but not at the expense of absolute sensitivity.     

Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.     

The structural basis of agonist-induced activation in constitutively active rhodopsin

G-protein-coupled receptors (GPCRs) comprise the largest family of membrane proteins in the human genome and mediate cellular responses to an extensive array of hormones, neurotransmitters and sensory stimuli. Although some crystal structures have been determined for GPCRs, most are for modified forms, showing little basal activity, and are bound to inverse agonists or antagonists. Consequently, these structures correspond to receptors in their inactive states. The visual pigment rhodopsin is the only GPCR for which structures exist that are thought to be in the active state. However, these structures are for the apoprotein, or opsin, form that does not contain the agonist all-trans retinal. Here we present a crystal structure at a resolution of 3 ? for the constitutively active rhodopsin mutant Glu 113 Gln in complex with a peptide derived from the carboxy terminus of the α-subunit of the G protein transducin. The protein is in an active conformation that retains retinal in the binding pocket after photoactivation. Comparison with the structure of ground-state rhodopsin suggests how translocation of the retinal β-ionone ring leads to a rotation of transmembrane helix 6, which is the critical conformational change on activation. A key feature of this conformational change is a reorganization of water-mediated hydrogen-bond networks between the retinal-binding pocket and three of the most conserved GPCR sequence motifs. We thus show how an agonist ligand can activate its GPCR.     

T-cell-mediated enhancement of host-versus-graft reactivity in mice fed a diet enriched in vitamin A acetate

Retinol (vitamin A) and some of its derivatives have an important role in: (1) regulating growth, proliferation and differentiation of various tissues and (2) maintaining reproduction and visual function in man and higher animals. Vitamin A and retinoids are also known as potent immunoregulatory and antineoplastic agents. Their ability to increase reactivity to histoincompatible tissues is well documented but the mechanism of this action is unclear. Here we report that mice fed on an otherwise conventional diet supplemented with vitamin A acetate (VAA) respond to 10(5) semiallogeneic cells (a suboptimal dose) in a host-versus-graft (HvG) reaction, whereas mice on a conventional diet do not. It is possible to transfer this enhanced immune reactivity by injecting lymphoid cells from VAA-fed animals into those syngeneic mice maintained on the conventional diet. Using a positive selection technique, we demonstrate that the phenotype of the cell probably responsible for this phenomenon is Lyt 1+ 2-.     

The response of the adrenal gland to hypoglycaemia in the conscious calf

Résumé La sécrétion de glucocorticoides et de catécholamines par la glande surrénale droite fut observée chez des veaux conscients après une injection d'insuline. L'accroissement de la production de stéroides fut passagère malgré une hypoglycémie ininterrompue.

---

---

Acknowledgements. This work was supported by grants from the Medical Research Council, the Smith, Kline & French Foundation and Twyford Pharmaceutical Services Ltd. We are also indebted to Dr.D. M. Burley (CIBA) for his continued assistance and to Dr.P. C. Risdall (Boots Co. Ltd.) who supplied the highly purified insulin. K.W.M. has been supported by the Agricultural Research Council. It is a particularly pleasure to acknowledge the skilled technical assistance provided by Mr.P.M.M. Bircham.