An amino-acid taste receptor

The sense of taste provides animals with valuable information about the nature and quality of food. Mammals can recognize and respond to a diverse repertoire of chemical entities, including sugars, salts, acids and a wide range of toxic substances. Several amino acids taste sweet or delicious (umami) to humans, and are attractive to rodents and other animals. This is noteworthy because L-amino acids function as the building blocks of proteins, as biosynthetic precursors of many biologically relevant small molecules, and as metabolic fuel. Thus, having a taste pathway dedicated to their detection probably had significant evolutionary implications. Here we identify and characterize a mammalian amino-acid taste receptor. This receptor, T1R1+3, is a heteromer of the taste-specific T1R1 and T1R3 G-protein-coupled receptors. We demonstrate that T1R1 and T1R3 combine to function as a broadly tuned L-amino-acid sensor responding to most of the 20 standard amino acids, but not to their D-enantiomers or other compounds. We also show that sequence differences in T1R receptors within and between species (human and mouse) can significantly influence the selectivity and specificity of taste responses.     

Dopamine-mediated modulation of odour-evoked amygdala potentials during pavlovian conditioning

Pavlovian conditioning results when an innocuous stimulus, such as an odour, is paired with a behaviourally relevant stimulus, such as a foot-shock, so that eventually the former stimulus alone will elicit the behavioural response of the latter. The lateral nucleus of the amygdala (LAT) is necessary for the emotional memory formation in this paradigm. Enhanced neuronal firing in LAT to conditioned stimuli emerge in parallel with the behavioural changes and are dependent on local dopamine. To study the changes in neuronal excitability and synaptic drive that contribute to the pavlovian conditioning process, here we used in vivo intracellular recordings to examine LAT neurons during pavlovian conditioning in rats. We found that repeated pairings of an odour with a foot-shock resulted in enhanced post-synaptic potential (PSP) responses to the odour and increased neuronal excitability. However, a non-paired odour displayed PSP decrement. The dopamine antagonist haloperidol blocked the PSP enhancement and associated increased neuronal excitability, without reversing previous conditioning. These results demonstrate that conditioning and habituation processes produce opposite effects on LAT neurons and that dopamine is important in these events, consistent with its role in emotional memory formation.     

Synthesis of N-(2-hydroxy-1-phenoxyacetyl) prolyproline

Ionophores consist of molecules which surround and carry positive metal ions and other ions through biological membranes. One classe of ionophores which we have been developing contains dipeptides which are encouraged to become part of a ring because of possible hydrogen bond formation between the 2-hydroxy on the phenyl group and carboxyl group (COOH) of the final amide proline. Formation of a ring should increase the complexation ability of the ionophore. We report that the synthesis of N-(2-hydroxyl-1-phenoxyacetyl) prolyproline(1), a novel ionophore is prepared from activated 2-acetoxy phenoxyacetic acid (3a) and the appropriate dipeptide ester using coupling methods such as dicyclohexyl carbodiimide with hydroxyben-ztriazole or carbonyl diimidazole. Yang Dingqiao: born in 1958, Associate professor     

Upper intestinal lipids regulate energy and glucose homeostasis

Upon the entry of nutrients into the small intestine, nutrient sensing mechanisms are activated to allow the body to adapt appropriately to the incoming nutrients. To date, mounting evidence points to the existence of an upper intestinal lipid-induced gut–brain neuronal axis to regulate energy homeostasis. Moreover, a recent discovery has also revealed an upper intestinal lipid-induced gut–brain–liver neuronal axis involved in the regulation of glucose homeostasis. In this mini-review, we will focus on the mechanisms underlying the activation of these respective neuronal axes by upper intestinal lipids.     

Nicotinamide/nicotinic acid mononucleotide adenylyltransferase, new insights into an ancient enzyme

Nicotinamide/nicotinic acid mononucleotide adenylyltransferase (NMNAT) has long been known as the master enzyme in NAD biosynthesis in living organisms. A burst of investigations on NMNAT, going beyond enzymology, have paralleled increasing discoveries of key roles played by NAD homeostasis in a number or patho-physiological conditions. The availability of in-depth kinetics and structural enzymology analyses carried out on NMNATs from different organisms offer a powerful tool for uncovering fascinating evolutionary relationships. On the other hand, additional functions featuring NMNAT have emerged from investigations aimed at unraveling the molecular mechanisms responsible for complex biological phenomena such as neurodegeneration. NMNAT appears to be a multifunctional protein that sits both at the core of central metabolism and at a crossroads of multiple cellular processes. The resultant wealth of biochemical data has built a robust framework upon which design of NMNAT activators, inhibitors or enzyme variants of potential medical interest can be based.     

Analysis of the DNA sequence and duplication history of human chromosome 15

Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplications in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome.     

Life in the Fas lane: differential outcomes of Fas signaling

Fas, also known as CD95 or APO-1, is a member of the tumor necrosis factor/nerve growth factor superfamily. Although best characterized in terms of its apoptotic function, recent studies have identified several other cellular responses emanating from Fas. These responses include migration, invasion, inflammation, and proliferation. In this review, we focus on the diverse cellular outcomes of Fas signaling and the molecular switches identified to date that regulate its pro- and anti-apoptotic functions. Such switches occur at different levels of signal transduction, ranging from the receptor through to cross-talk with other signaling pathways. Factors identified to date including other extracellular signals, proteins recruited to the death-inducing signaling complex, and the availability of different intracellular components of signal transduction pathways. The success of therapeutically targeting Fas will require a better understanding of these pathways, as well as the regulatory mechanisms that determine cellular outcome following receptor activation.     

Structure and stereochemistry of brianolide,a new antiinflammatory diterpenoid from the Okinawan gorgonianBriareum sp.

Summary Brianolide (1), a new antiinflammatory diterpenoid of the briarein class, possessing a substituent at C-12 (R), has been isolated from the Okinawan gorgonianBriareum sp. Its structure has been established from spectral data in conjunction with a single crystal X-ray analysis.     

浑沌：它能有多少规律

40年前A.爱因斯坦给M.玻恩的一封信中写道,“上帝不玩骰子。”爱因斯坦是始终反对量子论的概率解释的,他不倦地探索着与经典力学更为直接的类比,即考虑没有概率不定性的确定过程。如今,40年过去了,没有人会惊讶:甚至在一个经典哈密顿动力系统中也存在着(chas)在物理客体规则运动的领域内,在没有人预期会有的地方冒出