A single population of olfactory sensory neurons mediates an innate avoidance behaviour in Drosophila

All animals exhibit innate behaviours in response to specific sensory stimuli that are likely to result from the activation of developmentally programmed neural circuits. Here we observe that Drosophila exhibit robust avoidance to odours released by stressed flies. Gas chromatography and mass spectrometry identifies one component of this 'Drosophila stress odorant (dSO)' as CO2. CO2 elicits avoidance behaviour, at levels as low as 0.1%. We used two-photon imaging with the Ca2+-sensitive fluorescent protein G-CaMP to map the primary sensory neurons governing avoidance to CO2. CO2 activates only a single glomerulus in the antennal lobe, the V glomerulus; moreover, this glomerulus is not activated by any of 26 other odorants tested. Inhibition of synaptic transmission in sensory neurons that innervate the V glomerulus, using a temperature-sensitive Shibire gene (Shi(ts)), blocks the avoidance response to CO2. Inhibition of synaptic release in the vast majority of other olfactory receptor neurons has no effect on this behaviour. These data demonstrate that the activation of a single population of sensory neurons innervating one glomerulus is responsible for an innate avoidance behaviour in Drosophila.     

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.     

一种新型高效生物可降解ε-多聚赖氨酸修饰阳离子聚合物抗菌剂的合成与性能（英文）

目前临床上使用的大多数抗生素杀菌或抑菌的主要机制为:选择性的作用于细菌细胞核酸和蛋白合成系统的特定环节,妨碍细菌生命活动,导致细菌死亡.然而,细菌形态结构完整性仍然保持,导致细菌产生耐药性.最近研究发现大肠杆菌和金黄色葡萄球菌感染是一些慢性疾病发生的重要因素.纳米颗粒能够选择性的作用于微生物表面,破坏细菌结构完整性,抑制细菌耐药性的产生.本文设计并合成一种生物相容性好且生物可降解ε-多聚赖氨酸修饰阳离子聚合物(EPL-PCL).该多聚物能够自主装形成单分散的纳米颗粒,且对大肠杆菌、金黄色葡萄球菌和枯草芽孢杆菌具有广谱的抗菌活性.相比于ε-多聚赖氨酸,EPL-PCL纳米颗粒具有更强的抗菌活性.进一步研究发现,EPL-PCL纳米颗粒抗菌作用的主要机制为:(1)带正电的EPL-PCL纳米颗粒与带负电的细菌表面相互作用并穿透细胞壁和细胞膜,破坏细菌表面完整性,抑制细菌耐药性的生成;(2)EPL-PCL纳米颗粒暴露显著提高细菌内ROS水平;(3)ROS水平升高显著的破坏细菌细胞代谢,例如提高碱性磷酸酶活性破坏细菌磷的稳态平衡.因此,本文合成的可降解ε-多聚赖氨酸修饰阳离子纳米聚合物可以作为一种有效且广谱的抗菌剂,特别是用于病原菌感染的疾病.     

Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis

Haploinsufficiency of Dll4, a vascular-specific Notch ligand, has shown that it is essential for embryonic vascular development and arteriogenesis. Mechanistically, it is unclear how the Dll4-mediated Notch pathway contributes to complex vascular processes that demand meticulous coordination of multiple signalling pathways. Here we show that Dll4-mediated Notch signalling has a unique role in regulating endothelial cell proliferation and differentiation. Neutralizing Dll4 with a Dll4-selective antibody rendered endothelial cells hyperproliferative, and caused defective cell fate specification or differentiation both in vitro and in vivo. In addition, blocking Dll4 inhibited tumour growth in several tumour models. Remarkably, antibodies against Dll4 and antibodies against vascular endothelial growth factor (VEGF) had paradoxically distinct effects on tumour vasculature. Our data also indicate that Dll4-mediated Notch signalling is crucial during active vascularization, but less important for normal vessel maintenance. Furthermore, unlike blocking Notch signalling globally, neutralizing Dll4 had no discernable impact on intestinal goblet cell differentiation, supporting the idea that Dll4-mediated Notch signalling is largely restricted to the vascular compartment. Therefore, targeting Dll4 might represent a broadly efficacious and well-tolerated approach for the treatment of solid tumours.     

Functional connectivity in the retina at the resolution of photoreceptors

To understand a neural circuit requires knowledge of its connectivity. Here we report measurements of functional connectivity between the input and ouput layers of the macaque retina at single-cell resolution and the implications of these for colour vision. Multi-electrode technology was used to record simultaneously from complete populations of the retinal ganglion cell types (midget, parasol and small bistratified) that transmit high-resolution visual signals to the brain. Fine-grained visual stimulation was used to identify the location, type and strength of the functional input of each cone photoreceptor to each ganglion cell. The populations of ON and OFF midget and parasol cells each sampled the complete population of long- and middle-wavelength-sensitive cones. However, only OFF midget cells frequently received strong input from short-wavelength-sensitive cones. ON and OFF midget cells showed a small non-random tendency to selectively sample from either long- or middle-wavelength-sensitive cones to a degree not explained by clumping in the cone mosaic. These measurements reveal computations in a neural circuit at the elementary resolution of individual neurons.