Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40

Diabetes, a disease in which carbohydrate and lipid metabolism are regulated improperly by insulin, is a serious worldwide health issue. Insulin is secreted from pancreatic beta cells in response to elevated plasma glucose, with various factors modifying its secretion. Free fatty acids (FFAs) provide an important energy source as nutrients, and they also act as signalling molecules in various cellular processes, including insulin secretion. Although FFAs are thought to promote insulin secretion in an acute phase, this mechanism is not clearly understood. Here we show that a G-protein-coupled receptor, GPR40, which is abundantly expressed in the pancreas, functions as a receptor for long-chain FFAs. Furthermore, we show that long-chain FFAs amplify glucose-stimulated insulin secretion from pancreatic beta cells by activating GPR40. Our results indicate that GPR40 agonists and/or antagonists show potential for the development of new anti-diabetic drugs.     

Evidence from fluid inclusions for microbial methanogenesis in the early Archaean era

Methanogenic microbes may be one of the most primitive organisms, although it is uncertain when methanogens first appeared on Earth. During the Archaean era (before 2.5 Gyr ago), methanogens may have been important in regulating climate, because they could have provided sufficient amounts of the greenhouse gas methane to mitigate a severely frozen condition that could have resulted from lower solar luminosity during these times. Nevertheless, no direct geological evidence has hitherto been available in support of the existence of methanogens in the Archaean period, although circumstantial evidence is available in the form of approximately 2.8-Gyr-old carbon-isotope-depleted kerogen. Here we report crushing extraction and carbon isotope analysis of methane-bearing fluid inclusions in approximately 3.5-Gyr-old hydrothermal precipitates from Pilbara craton, Australia. Our results indicate that the extracted fluids contain microbial methane with carbon isotopic compositions of less than -56 per thousand included within original precipitates. This provides the oldest evidence of methanogen (> 3.46 Gyr ago), pre-dating previous geochemical evidence by about 700 million years.     

日本那须地区人工草地牧草生物量随时间变化的解析——Ⅰ地上生物量(英文)

为了揭示草地生态系统的现存生物量随时间的变化规律与气候条件和人为干扰(放牧压,施肥量等)之间的关系,从1974年开始至1994年,每年的4月至11月,在位于日本中部那须地区的国立草地研究所内的人造围栏放牧草场进行了放牧试验.结果表明,在1974至1994年的21年间,在不同放牧处理(放牧压分别为轻度和重度/施肥分少量和大量)的条件下,地上现存生物量的季节变化非常明显,其变化范围为:150～380gDWm-2.用4次方多项式检验表明牧草成长模式呈双峰曲线,每一年中不同放牧条件下地上现存生物量的最大值都出现在6月份左右,第二个峰值出现在9,10月份.复合回归分析的结果得出了体现现存生物量和气温,放牧压(或施肥量)之间的定量关系的多项回归方程式.协方差分析结果表明放牧压力,施肥量以及季节和年度的变化,以及他们之间的相互作用对现存生物量有着显著影响(P<0.05)或极显著影响(P<0.01).本研究表明在现存放牧强度下不会对地上生物量造成毁灭性的影响,而是在其承受范围之内.     

Deformation and rupture of the oceanic crust may control growth of Hawaiian volcanoes

Hawaiian volcanoes are formed by the eruption of large quantities of basaltic magma related to hot-spot activity below the Pacific Plate. Despite the apparent simplicity of the parent process--emission of magma onto the oceanic crust--the resulting edifices display some topographic complexity. Certain features, such as rift zones and large flank slides, are common to all Hawaiian volcanoes, indicating similarities in their genesis; however, the underlying mechanism controlling this process remains unknown. Here we use seismological investigations and finite-element mechanical modelling to show that the load exerted by large Hawaiian volcanoes can be sufficient to rupture the oceanic crust. This intense deformation, combined with the accelerated subsidence of the oceanic crust and the weakness of the volcanic edifice/oceanic crust interface, may control the surface morphology of Hawaiian volcanoes, especially the existence of their giant flank instabilities. Further studies are needed to determine whether such processes occur in other active intraplate volcanoes.     

CD38 is critical for social behaviour by regulating oxytocin secretion

CD38, a transmembrane glycoprotein with ADP-ribosyl cyclase activity, catalyses the formation of Ca2+ signalling molecules, but its role in the neuroendocrine system is unknown. Here we show that adult CD38 knockout (CD38-/-) female and male mice show marked defects in maternal nurturing and social behaviour, respectively, with higher locomotor activity. Consistently, the plasma level of oxytocin (OT), but not vasopressin, was strongly decreased in CD38-/- mice. Replacement of OT by subcutaneous injection or lentiviral-vector-mediated delivery of human CD38 in the hypothalamus rescued social memory and maternal care in CD38-/- mice. Depolarization-induced OT secretion and Ca2+ elevation in oxytocinergic neurohypophysial axon terminals were disrupted in CD38-/- mice; this was mimicked by CD38 metabolite antagonists in CD38+/+ mice. These results reveal that CD38 has a key role in neuropeptide release, thereby critically regulating maternal and social behaviours, and may be an element in neurodevelopmental disorders.     

Large scale cDNA sequencing for analysis of quantitative and qualitative aspects of gene expression.

Large scale sequencing of cDNAs provides a complementary approach to structural analysis of the human genome by generating expressed sequence tags (ESTs). We have initiated the large-scale sequencing of a 3'-directed cDNA library from the human liver cell line HepG2, that is a non-biased representation of the mRNA population. 982 random cDNA clones were sequenced yielding more than 270 kilobases. A significant portion of the identified genes encoded secretable proteins and components for protein-synthesis. The abundance of cDNA species varied from 2.2% to less than 0.004%. Fifty two percent of the mRNA were abundant species consisting of 173 genes and the rest were non-abundant, consisting of about 6,600 genes.     

Preferential cis-syn thymine dimer bypass by DNA polymerase eta occurs with biased fidelity

Human DNA polymerase eta (Pol eta) modulates susceptibility to skin cancer by promoting DNA synthesis past sunlight-induced cyclobutane pyrimidine dimers that escape nucleotide excision repair (NER). Here we have determined the efficiency and fidelity of dimer bypass. We show that Pol eta copies thymine dimers and the flanking bases with higher processivity than it copies undamaged DNA, and then switches to less processive synthesis. This ability of Pol eta to sense the dimer location as synthesis proceeds may facilitate polymerase switching before and after lesion bypass. Pol eta bypasses a dimer with low fidelity and with higher error rates at the 3' thymine than at the 5' thymine. A similar bias is seen with Sulfolobus solfataricus DNA polymerase 4, which forms a Watson-Crick base pair at the 3' thymine of a dimer but a Hoogsteen base pair at the 5' thymine (ref. 3). Ultraviolet-induced mutagenesis is also higher at the 3' base of dipyrimidine sequences. Thus, in normal people and particularly in individuals with NER-defective xeroderma pigmentosum who accumulate dimers, errors made by Pol eta during dimer bypass could contribute to mutagenesis and skin cancer.     

The use of earthquake rate changes as a stress meter at Kilauea volcano

Stress changes in the Earth's crust are generally estimated from model calculations that use near-surface deformation as an observational constraint. But the widespread correlation of changes of earthquake activity with stress has led to suggestions that stress changes might be calculated from earthquake occurrence rates obtained from seismicity catalogues. Although this possibility has considerable appeal, because seismicity data are routinely collected and have good spatial and temporal resolution, the method has not yet proven successful, owing to the non-linearity of earthquake rate changes with respect to both stress and time. Here, however, we present two methods for inverting earthquake rate data to infer stress changes, using a formulation for the stress- and time-dependence of earthquake rates. Application of these methods at Kilauea volcano, in Hawaii, yields good agreement with independent estimates, indicating that earthquake rates can provide a practical remote-sensing stress meter.