Cortical remodelling induced by activity of ventral tegmental dopamine neurons.

Representations of sensory stimuli in the cerebral cortex can undergo progressive remodelling according to the behavioural importance of the stimuli. The cortex receives widespread projections from dopamine neurons in the ventral tegmental area (VTA), which are activated by new stimuli or unpredicted rewards, and are believed to provide a reinforcement signal for such learning-related cortical reorganization. In the primary auditory cortex (AI) dopamine release has been observed during auditory learning that remodels the sound-frequency representations. Furthermore, dopamine modulates long-term potentiation, a putative cellular mechanism underlying plasticity. Here we show that stimulating the VTA together with an auditory stimulus of a particular tone increases the cortical area and selectivity of the neural responses to that sound stimulus in AI. Conversely, the AI representations of nearby sound frequencies are selectively decreased. Strong, sharply tuned responses to the paired tones also emerge in a second cortical area, whereas the same stimuli evoke only poor or non-selective responses in this second cortical field in naive animals. In addition, we found that strong long-range coherence of neuronal discharge emerges between AI and this secondary auditory cortical area.     

Sound-induced motility of isolated cochlear outer hair cells is frequency-specific

The inner ear is capable of highly selective frequency discrimination. This is achieved not only by the travelling wave of the basilar membrane in the cochlear partition, but also by the active participation of nonlinear and vulnerable elements that enhance frequency selectivity. It has been shown that isolated mammalian outer hair cells respond with a change in length when subjected to sound stimulation at a fixed frequency. Here we investigate the motile behaviour of isolated cells when the stimulus frequency is varied between 200 and 10,000 Hz. By varying the frequency and the intensity of the tone, it is possible to obtain 'tuning curves' for the motile response. We demonstrate that the cell body of solitary hair cells, free from contact with the basilar membrane, shows a sharply tuned motile behaviour. We suggest that frequency selectivity in the organ of Corti is amplified by the tuned motility of the cell body of outer hair cells.     

Stereocilin-deficient mice reveal the origin of cochlear waveform distortions

Although the cochlea is an amplifier and a remarkably sensitive and finely tuned detector of sounds, it also produces conspicuous mechanical and electrical waveform distortions. These distortions reflect nonlinear mechanical interactions within the cochlea. By allowing one tone to suppress another (masking effect), they contribute to speech intelligibility. Tones can also combine to produce sounds with frequencies not present in the acoustic stimulus. These sounds compose the otoacoustic emissions that are extensively used to screen hearing in newborns. Because both cochlear amplification and distortion originate from the outer hair cells-one of the two types of sensory receptor cells-it has been speculated that they stem from a common mechanism. Here we show that the nonlinearity underlying cochlear waveform distortions relies on the presence of stereocilin, a protein defective in a recessive form of human deafness. Stereocilin was detected in association with horizontal top connectors, lateral links that join adjacent stereocilia within the outer hair cell's hair bundle. These links were absent in stereocilin-null mutant mice, which became progressively deaf. At the onset of hearing, however, their cochlear sensitivity and frequency tuning were almost normal, although masking was much reduced and both acoustic and electrical waveform distortions were completely lacking. From this unique functional situation, we conclude that the main source of cochlear waveform distortions is a deflection-dependent hair bundle stiffness resulting from constraints imposed by the horizontal top connectors, and not from the intrinsic nonlinear behaviour of the mechanoelectrical transducer channel.     

Ionic basis of membrane potential in outer hair cells of guinea pig cochlea

Mammalian hearing involves features not found in other species, for example, the separation of sound frequencies depends on an active control of the cochlear mechanics. The force-generating component in the cochlea is likely to be the outer hair cell (OHC), one of the two types of sensory cell through which current is gated by mechano-electrical transducer channels sited on the apical surface. Outer hair cells isolated in vitro have been shown to be motile and capable of generating forces at acoustic frequencies. The OHC membrane is not, however, electrically tuned, as found in lower vertebrates. Here we describe how the OHC resting potential is determined by a Ca2+-activated K+ conductance at the base of the cell. Two channel types with unitary sizes of 240 and 45 pS underlie this Ca2+-activated K+ conductance and we suggest that their activity is determined by a Ca2+ influx through the apical transducer channel, as demonstrated in other hair cells. This coupled system simultaneously explains the large OHC resting potentials observed in vivo and indicates how the current gated by the transducer may be maximized to generate the forces required in cochlear micromechanics.     

Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier

Hearing sensitivity in mammals is enhanced by more than 40 dB (that is, 100-fold) by mechanical amplification thought to be generated by one class of cochlear sensory cells, the outer hair cells. In addition to the mechano-electrical transduction required for auditory sensation, mammalian outer hair cells also perform electromechanical transduction, whereby transmembrane voltage drives cellular length changes at audio frequencies in vitro. This electromotility is thought to arise through voltage-gated conformational changes in a membrane protein, and prestin has been proposed as this molecular motor. Here we show that targeted deletion of prestin in mice results in loss of outer hair cell electromotility in vitro and a 40-60 dB loss of cochlear sensitivity in vivo, without disruption of mechano-electrical transduction in outer hair cells. In heterozygotes, electromotility is halved and there is a twofold (about 6 dB) increase in cochlear thresholds. These results suggest that prestin is indeed the motor protein, that there is a simple and direct coupling between electromotility and cochlear amplification, and that there is no need to invoke additional active processes to explain cochlear sensitivity in the mammalian ear.     

Direct measurement of intra-cochlear pressure waves

The cochlear travelling wave is fundamental to the ability of the mammalian auditory system to resolve frequency. The seashell-shaped outer bone of the cochlea (the auditory inner ear) contains a spiral of cochlear fluid and the sensory tissue known as the cochlear partition. Sound travels down the ear canal to the eardrum, causing its flexible tympanic membrane to vibrate. This vibration is transmitted to the cochlea via the ossides. Motion of the stapes (the stirrup ossicle) sets the cochlear fluid in motion, which in turn sets the cochlear partition near the states in motion. The motion of the cochlear partition ripples down the cochlear spiral as a travelling wave, stimulating the cochlea's sensory hair cells. The wave peaks near the base (the stapes end) of the cochlea for high frequency tones and near the apex for low frequencies. The fundamental elements of the cochlear travelling wave are fluid pressure and motion and partition forces and motion. However, the wave's direct experimental study has to date relied almost solely on measurements of the partition motion. Here I report finely spaced measurements of intracochlear pressure close to the partition, which reveal the fluid component of the cochlear wave. The penetration depth of the wave is very limited, approximately 15 microm. Over a range of frequencies at least an octave wide, the depth is independent of frequency.     

Capacity of purified Lyt-2+ T cells to mount primary proliferative and cytotoxic responses to Ia- tumour cells

Allogeneic gene products of the major histocompatibility complex, the HLA complex in man and the H-2 complex in mice, induce T lymphocytes to exert powerful mixed lymphocyte reactions (MLR) and cell-mediated lympholysis (CML). In mice, the subset of T cells carrying the L3T4 surface antigen but lacking the Lyt-2 antigen responds predominantly to H-2 class II (Ia) differences whereas the L3T4- Lyt-2+ subset reacts to class I (K/D) differences. For primary responses the stimulus for MLR and CML appears to be controlled by Ia+ cells of the macrophage/dendritic cell lineages, for both L3T4+ and Lyt-2+ cells. The finding that Ia+ cells are required for responses involving Lyt-2+ cells has been taken to imply that triggering of these cells is controlled by Ia-restricted L3T4+ cells. Lyt-2+ cells have thus come to be regarded as crippled cells which are heavily dependent on 'help' from other T cells. This well-entrenched view is challenged by evidence presented here that purified Lyt-2+ cells can give high primary responses to certain Ia- tumour cells in vitro.     

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.     

Sr3AlO4F晶体中掺杂Ba2+,Ca2+离子占据不同Sr2+格位倾向性的第一性原理研究

通过比较第一性原理计算总能量得出碱金属离子Ba2+和Ca2+取代占据氟氧化物晶体Sr3AlO4F中两种不同Sr格位时,Ba2+倾向占据10配位的Sr(1)位,而Ca2+倾向占据8配位的Sr(2)位,与实验分析结果一致.基于上述优化结构,通过键价求和计算和畸变指数分析,得出Sr3AlO4F中Sr(1)格位离子严重未饱和成键,倾向于被较大Ba2+离子取代占据;而Sr(2)格位离子略微过饱和成键,倾向于被较小Ca2+离子取代占据.     

Force generation by mammalian hair bundles supports a role in cochlear amplification

It is generally accepted that the acute sensitivity and frequency discrimination of mammalian hearing requires active mechanical amplification of the sound stimulus within the cochlea. The prevailing hypothesis is that this amplification stems from somatic electromotility of the outer hair cells attributable to the motor protein prestin. Thus outer hair cells contract and elongate in synchrony with the sound-evoked receptor potential. But problems arise with this mechanism at high frequencies, where the periodic component of the receptor potential will be attenuated by the membrane time constant. On the basis of work in non-mammalian vertebrates, force generation by the hair bundles has been proposed as an alternative means of boosting the mechanical stimulus. Here we show that hair bundles of mammalian outer hair cells can also produce force on a submillisecond timescale linked to adaptation of the mechanotransducer channels. Because the bundle motor may ultimately be limited by the deactivation rate of the channels, it could theoretically operate at high frequencies. Our results show the existence of another force generator in outer hair cells that may participate in cochlear amplification.     

一类恒等函数问题的研究

设f:N→R+∪{0},g:N→C是完全积性函数,若f(p+1)=g(p)+1和f(p~2+q~3)=g(p~2)+g(q~3)对所有素数p,q均成立,则对所有素数p,q,π,f(p+1)=f(p~2+q~3)=0,g(π)=-1,或者对所有正整数n,f(n)=g(n)=n.     

一类固定系数解析函数的极值点与支撑点

摘要 设Q={f(z):f(z)=z-an+1zn+1-(∞∑k=n+2)akzk},这里an+1=c(n+2)/(n+1)(n+3),ak≥0,∞∑k=n+2k(k+2)/k+1ak≤1-c,0≤c≤1,n∈N,并且f(z)在单位圆盘△={z:| z |＜1}内解析,得到函数族Q的极值点与支撑点.     

Forces between clustered stereocilia minimize friction in the ear on a subnanometre scale

The detection of sound begins when energy derived from an acoustic stimulus deflects the hair bundles on top of hair cells. As hair bundles move, the viscous friction between stereocilia and the surrounding liquid poses a fundamental physical challenge to the ear's high sensitivity and sharp frequency selectivity. Part of the solution to this problem lies in the active process that uses energy for frequency-selective sound amplification. Here we demonstrate that a complementary part of the solution involves the fluid-structure interaction between the liquid within the hair bundle and the stereocilia. Using force measurement on a dynamically scaled model, finite-element analysis, analytical estimation of hydrodynamic forces, stochastic simulation and high-resolution interferometric measurement of hair bundles, we characterize the origin and magnitude of the forces between individual stereocilia during small hair-bundle deflections. We find that the close apposition of stereocilia effectively immobilizes the liquid between them, which reduces the drag and suppresses the relative squeezing but not the sliding mode of stereociliary motion. The obliquely oriented tip links couple the mechanotransduction channels to this least dissipative coherent mode, whereas the elastic horizontal top connectors that stabilize the structure further reduce the drag. As measured from the distortion products associated with channel gating at physiological stimulation amplitudes of tens of nanometres, the balance of viscous and elastic forces in a hair bundle permits a relative mode of motion between adjacent stereocilia that encompasses only a fraction of a nanometre. A combination of high-resolution experiments and detailed numerical modelling of fluid-structure interactions reveals the physical principles behind the basic structural features of hair bundles and shows quantitatively how these organelles are adapted to the needs of sensitive mechanotransduction.     

布依族9项头面部群体遗传学特征的研究

调查了布依族中学生320例(男172例，女148例)9项遗传学指标(内眦褶、上眼睑皱褶、门齿类型、鼻梁类型、鼻孔形状、下颏类型、耳垂类型、额头发际、发形)．结果显示：(1)布依族有内眦褶率较低．有上眼睑皱褶率较高，铲型门齿率中等偏高．凸鼻梁率中等水平，宽鼻孔率较高．突型下颏率中等偏高，有耳垂率中等偏低，额头发际有尖率较低，卷发率较低；(2)除了内眦褶、耳垂类型外，其余7项指标类型出现率性别间均无显著差异；(3)9项指标彼此间相关性极小；(4)总的来看，与其他人群7项特征基因频率比较的结果显示：布依族与汉族、蒙古族、朝鲜族、达斡尔族、鄂温克族、鄂伦春族在内眦褶、上眼睑皱褶、鼻孔形状、额头发际这4项指标的基因频率上大多存在极显著性差异．     

凉水、丰林国家自然保护区红松遗传多样性的ISSR分析

采用了ISSR分子标记技术对凉水和丰林地区的两个红松种群的74个个体进行了遗传多样性分析．13个随机引物共检测到103个可重复的位点，其中82个具有多态性。多态位点百分比分别为73．79％和71．84％．Shannon信息指数和Nei指数的统计结果都表明，红松的遗传多样性凉水种群大于丰林种群。红松种内的遗传变异主要存在于群体内，种群内存在一定的遗传分化．     

关于约数和的一个不等式

对于正整数k和n设δ(k)是k的不同约数之和,f(n)=δ(1)+δ(2)+…+δ(n).证明了:存在无穷多个正整数n,使得δ(f(n))≥n(n+1).     

一类p-叶算子值解析函数的性质(Ⅱ)

引入一类p-叶算子值解析函数Rβ^b(A,B),对于任一f(z)∈Rβ^b(A,B)具有如下形式：f(z)=z^p ∑n=1^∞An p^z^n p(z∈△,An p∈B（H））。对这类算子值函数的系数作出精确的估计,并给出此类函数的一个必要条件和一个充分条件及变形定理。     

亚纯函数及其导数分担小函数集的唯一性

研究了亚纯函数及其k阶导数权分担小函数集的唯一性,得到了:设k,n为正整数,f,g为开平面上超越亚纯函数,以∞为IM公共值,E(S1,f)=E(S1,g)且E1(S2,f(k))=E1(S2,g(k)l(≥2)∈N如果2nδ2+k(an,fn)+(nk+4)Θ(∞,f)n(k+1)+4则f≡tg(tn=1)或[f(k)n(akn)][(gkn)(akn)]=]bn-(akn])2,并且文中还讨论了当l=0,1时的情形.这些定理推广和改进了先前的一些结果.