The role of Drosophila Piezo in mechanical nociception

Transduction of mechanical stimuli by receptor cells is essential for senses such as hearing, touch and pain. Ion channels have a role in neuronal mechanotransduction in invertebrates; however, functional conservation of these ion channels in mammalian mechanotransduction is not observed. For example, no mechanoreceptor potential C (NOMPC), a member of transient receptor potential (TRP) ion channel family, acts as a mechanotransducer in Drosophila melanogaster and Caenorhabditis elegans; however, it has no orthologues in mammals. Degenerin/epithelial sodium channel (DEG/ENaC) family members are mechanotransducers in C. elegans and potentially in D. melanogaster; however, a direct role of its mammalian homologues in sensing mechanical force has not been shown. Recently, Piezo1 (also known as Fam38a) and Piezo2 (also known as Fam38b) were identified as components of mechanically activated channels in mammals. The Piezo family are evolutionarily conserved transmembrane proteins. It is unknown whether they function in mechanical sensing in vivo and, if they do, which mechanosensory modalities they mediate. Here we study the physiological role of the single Piezo member in D. melanogaster (Dmpiezo; also known as CG8486). Dmpiezo expression in human cells induces mechanically activated currents, similar to its mammalian counterparts. Behavioural responses to noxious mechanical stimuli were severely reduced in Dmpiezo knockout larvae, whereas responses to another noxious stimulus or touch were not affected. Knocking down Dmpiezo in sensory neurons that mediate nociception and express the DEG/ENaC ion channel pickpocket (ppk) was sufficient to impair responses to noxious mechanical stimuli. Furthermore, expression of Dmpiezo in these same neurons rescued the phenotype of the constitutive Dmpiezo knockout larvae. Accordingly, electrophysiological recordings from ppk-positive neurons revealed a Dmpiezo-dependent, mechanically activated current. Finally, we found that Dmpiezo and ppk function in parallel pathways in ppk-positive cells, and that mechanical nociception is abolished in the absence of both channels. These data demonstrate the physiological relevance of the Piezo family in mechanotransduction in vivo, supporting a role of Piezo proteins in mechanosensory nociception.     

盐生杜氏藻碱性蛋白的研究

以一种单细胞的盐生杜氏藻为实验材料，利用化学和机械的方法破碎细胞，然后梯度分离细胞核，用盐酸抽提细胞核蛋白质，并与小牛胸腺组蛋白相比较。用ＳＤＳ－ＰＡＧＥ分析测定所得的碱性蛋白发现盐生杜氏藻核中有三条碱性蛋白带，两条蛋白带与Ｈ３与Ｈ４相对应，另一条分子量很小。     

Auditory collusion and a coupled couple of outer hair cells.

The discrepancies between measured frequency responses of the basilar membrane in the inner ear and the frequency tuning found in psychophysical experiments led to Bekesy's idea of lateral inhibition in the auditory nervous system. We now know that basilar membrane tuning can account for neural tuning, and that sharpening of the passive travelling wave depends on the mechanical activity of outer hair cells (OHCs)3, but the mechanism by which OHCs enhance tuning remains unclear. OHCs generate voltage-dependent length changes at acoustic rates, which deform the cochlear partition. Here we use an electrical correlate of OHC mechanical activity, the motility-related gating current, to investigate mechano-electrical interactions among adjacent OHCs. We show that the motility caused by voltage stimulation of one cell in a group evokes gating currents in adjacent OHCs. The resulting polarization in adjacent cells is opposite to that within the stimulated cell, which may be indicative of lateral inhibition. Also such interactions promote distortion and suppression in the electrical and, consequently, the mechanical activity of OHCs. Lateral interactions may provide a basis for enhanced frequency selectivity in the basilar membrane of mammals.     

A stomatin-domain protein essential for touch sensation in the mouse

Touch and mechanical pain are first detected at our largest sensory surface, the skin. The cell bodies of sensory neurons that detect such stimuli are located in the dorsal root ganglia, and subtypes of these neurons are specialized to detect specific modalities of mechanical stimuli. Molecules have been identified that are necessary for mechanosensation in invertebrates but so far not in mammals. In Caenorhabditis elegans, mec-2 is one of several genes identified in a screen for touch insensitivity and encodes an integral membrane protein with a stomatin homology domain. Here we show that about 35% of skin mechanoreceptors do not respond to mechanical stimuli in mice with a mutation in stomatin-like protein 3 (SLP3, also called Stoml3), a mammalian mec-2 homologue that is expressed in sensory neurons. In addition, mechanosensitive ion channels found in many sensory neurons do not function without SLP3. Tactile-driven behaviours are also impaired in SLP3 mutant mice, including touch-evoked pain caused by neuropathic injury. SLP3 is therefore indispensable for the function of a subset of cutaneous mechanoreceptors, and our data support the idea that this protein is an essential subunit of a mammalian mechanotransducer.     

Mechanosensitivity of mammalian auditory hair cells in vitro

Intracellular responses recorded in vitro from the cochleas of anaesthetized mammals have shown that the mechanoreceptive inner and outer hair cells are sharply tuned, accounting for many of the properties of the afferent fibres in the auditory nerve. However, in vivo it has not been possible to measure directly the excitatory mechanical input to these cells (the displacement of their mechanosensitive stereocilia) and thus to determine the relationship between the receptor potentials and displacement of their stereocilia. As a means of circumventing this technical difficulty, we have developed an organ culture of the mouse cochlea and here we describe the receptor potentials generated by the hair cells in response to direct displacement of their stereocilia.     

大中型兽类踪迹在野外考察及研究中的应用

在野外兽类考察过程中，由于多数兽类喜欢展昏活动或昼伏夜出，加上一些外界因素的影响，工作人员要对兽类进行直接的目的性观察和持续性研究有一定的难度．但由于动物的某些生物学特性，不同兽类的活动会在野外留下特定的踪迹，这为野外鉴别、观察和研究提供了重要的线索．本文总结了影响对大中型兽类进行直接性观察的因素、野外兽类踪迹的表现形式以及兽类的野外遗留物在有关研究中的应用，以期为野外考察与研究提供一定帮助．     

A new eutriconodont mammal and evolutionary development in early mammals

Detachment of the three tiny middle ear bones from the reptilian mandible is an important innovation of modern mammals. Here we describe a Mesozoic eutriconodont nested within crown mammals that clearly illustrates this transition: the middle ear bones are connected to the mandible via an ossified Meckel's cartilage. The connected ear and jaw structure is similar to the embryonic pattern in modern monotremes (egg-laying mammals) and placental mammals, but is a paedomorphic feature retained in the adult, unlike in monotreme and placental adults. This suggests that reversal to (or retention of) this premammalian ancestral condition is correlated with different developmental timing (heterochrony) in eutriconodonts. This new eutriconodont adds to the evidence of homoplasy of vertebral characters in the thoraco-lumbar transition and unfused lumbar ribs among early mammals. This is similar to the effect of homeobox gene patterning of vertebrae in modern mammals, making it plausible to extrapolate the effects of Hox gene patterning to account for homoplastic evolution of vertebral characters in early mammals.     

Common mammals drive the evolutionary increase of hypsodonty in the Neogene

During the past 20 million years, herbivorous mammals of numerous lineages have evolved hypsodont, or high-crowned, cheek teeth. Hypsodonty is informative ecologically because it is well developed in mammals eating fibrous and abrasive foods that are most abundant in open and generally or seasonally dry environments. Here we report that in the Neogene of Europe mammals with the greatest locality coverages showed an increase in hypsodonty. We used a data set of 209 localities to measure whether large mammals occurring in many fossil localities show a similar increase in hypsodonty to mammals occurring in single or few localities. Taxonomic and morphological groupings show a low average hypsodonty in the early Miocene epoch. From the middle Miocene onwards, only the hypsodonty of commonly found mammals shows a marked increase. Therefore, in the drying Europe of the late Miocene, only increasingly hypsodont mammals may have been able to expand their share of habitats and food resources. These results suggest that the relatively small number of species known from multiple localities are palaeoecologically informative by themselves, irrespective of the rest of the known species.     

贵州省赤水桫椤自然保护区兽类的初步研究

2003年11月9日～18日对贵州赤水桫椤自然保护区兽类进行了初步调查和采集,共采获兽类标本10余号,经鉴定和分类,加上原有资料的记载,该保护区共有60种兽类,隶属8目21科45属,其中国家重点保护野生动物Ⅰ级3种,Ⅱ级11种。从区系组成看,以东洋界种为主体,共45种,占保护区兽类种数的75％。分布型以东南亚热带-亚热带型为主,有35种,占保护区兽类种数的58.3％,中国特有种有6种,占保护区兽类种数的10％。此外,易危兽类有13种,濒危兽类有3种,稀有兽类有1种。分别占中国濒危动物的9.8％,2.3％和0.75％。