Light adaptation in cone vision involves switching between receptor and post-receptor sites

We see over an enormous range of mean light levels, greater than the range of output signals retinal neurons can produce. Even highlights and shadows within a single visual scene can differ approximately 10,000-fold in intensity-exceeding the range of distinct neural signals by a factor of approximately 100. The effectiveness of daylight vision under these conditions relies on at least two retinal mechanisms that adjust sensitivity in the approximately 200 ms intervals between saccades. One mechanism is in the cone photoreceptors (receptor adaptation) and the other is at a previously unknown location within the retinal circuitry that benefits from convergence of signals from multiple cones (post-receptor adaptation). Here we find that post-receptor adaptation occurs as signals are relayed from cone bipolar cells to ganglion cells. Furthermore, we find that the two adaptive mechanisms are essentially mutually exclusive: as light levels increase the main site of adaptation switches from the circuitry to the cones. These findings help explain how human cone vision encodes everyday scenes, and, more generally, how sensory systems handle the challenges posed by a diverse physical environment.     

Relation of an array of early-differentiating cones to the photoreceptor mosaic in the primate retina.

The retina of diurnal primates, including humans, contains a reiterative mosaic of red-, green- and blue-sensitive cones whose visual pigments are maximally sensitive to long, middle or short wavelengths, respectively. Although the distribution of the cone subtypes in the adult rhesus monkey has been quantified using opsin-specific antisera, the mechanism for the phenotypic specification of the cone subtypes and the establishment of their ratios in the retinal mosaic remain unknown. Here we present immunocytochemical evidence that a subset of cones (about 10%) express their cell-specific opsin two to three weeks before the surrounding cones. Remarkably, these precocious cones are evenly stationed throughout undifferentiated regions of the retinal surface from several weeks after their last mitotic division, and at least one month before the formation of their synapses with bipolar and horizontal cells. Use of confocal laser microscopy reveals that the inner segments of immunolabelled and surrounding unlabelled cones are transiently in apposition with one another, enabling surface mediated interactions to occur during this period. We suggest that the early maturing cones induce neighbouring undifferentiated cones to express an appropriate opsin phenotype, and therefore constitute a 'protomap' for the emergence of the species-specific retinal mosaic.     

Disoriented pathfinding by pioneer neurone growth cones deprived of filopodia by cytochalasin treatment

A major question in developmental neurobiology is how developing nerve cells accurately extend processes to establish connections with their target cells. This problem involves both the nature of cues for growth cone guidance and also the question of how growth cones survey their environment for cues and respond by altering their direction of migration. The filopodia which normally extend from neuronal growth cones have been shown to affect growth cone steering in vitro and it has been proposed that they function in vivo in the detection of and response to guidance cues. This hypothesis could be tested in vivo if growth cones which normally have filopodia could be induced to migrate in their absence. The pair of Ti1 neurones are the first neurones to extend axons through the limb buds of embryonic grasshoppers. We report here an examination of the migration of Ti1 pioneer growth cones deprived of filopodia by culture in agents which disrupt actin microfilaments. Under these conditions, axons continue to extend but a large percentage of growth cones are highly disoriented. Our results indicate that Ti1 filopodia are not necessary for axonal elongation in vivo but that they are important for correctly oriented growth cone steering.     

马尾松二代育种群体生长和开花结实性状

对马尾松二代核心育种群体内亲本无性系的树高、胸径等生长性状及开花量、结实量等生殖性状进行了全面调查和分析。51个马尾松二代亲本无性系7年生时平均树高、胸径和材积分别为5.53 m、9.05 cm和0.021 m3,各生长性状在无性系之间的差异显著,各性状的无性系重复力较高。对进入开花结实盛期的39个无性系调查发现,开花量、结实量等生殖性状在不同亲本无性系之间的变异程度比生长性状的高。基于主要生长性状、生殖性状,将39个亲本无性系聚在4个类群内,不同类群存在显著性状差异:类群1生长性状总体较优,雌球花、球果量也较多;类群2生长性状总体较差,开花、球果量也较少;类群3生长性状较优、雄球花数量较多,但雌球花、球果数量较少;类群4生长性状总体较差,但雌球花、球果数多。无性系的雌球花、球果数与生长量呈弱度负相关,因而在选择杂交亲本或种子园建园亲本时,有必要在开展亲本配合力测评的同时,开展亲本的多性状选择,选出28个生长、生殖性状较为均衡(生长量、开花结实量均在中等或中等以上)的无性系,其单株雄球花数、球果数和单株材积分别比参试群体均值高18.2%,8.0%和9.6%。可将这些无性系作为候选优良亲本,结合亲本配合力的测评,从中选择优良的杂交亲本及二代种子园的建园材料。     

A presynaptic action of glutamate at the cone output synapse

Neurotransmitter release from many central nervous system synapses is regulated by 'autoreceptors' at the synaptic terminal, which bind the released transmitter and alter release accordingly. The photoreceptors of lower vertebrates are thought to use glutamate as a neurotransmitter. Glutamate conveys the visual signal to postsynaptic bipolar and horizontal cells, but has been reported not to act on the photoreceptors themselves. We show here that glutamate evokes a current, carried largely by chloride ions, in cones isolated from the tiger salamander retina. This response is localized to the synaptic terminal of the cone. Removing external sodium blocks this action of glutamate. These results suggest the existence of a positive feedback loop at the cone output synapse: over most of the light-response range, glutamate released by depolarization of the cone will cause further depolarization, increasing the gain of phototransduction. Glutamate released from rods may also polarize cones, modulating the gain of the cone output synapse. This system is surprisingly different from the autoreceptor systems for most other transmitters, which act in a negative feedback way.     

Multiple classes of glutamate receptor on depolarizing bipolar cells in retina

Multiple subtypes of excitatory amino acid receptor have been found on individual dissociated neurones. These findings were obtained from cells without intact synaptic connections, so the functional roles for such receptor subtypes are unknown. We have recorded intracellular responses from depolarizing bipolar cells (DBC) that receive direct synaptic input from two distinct populations of neurones: rods and cones. We report here that 2-amino-4-phosphonobutyrate (APB), a glutamate analogue, reveals two subtypes of glutamate receptors on DBCs. APB acts on the same receptor that mediates synaptic transmission from rods but has no action on the second subtype of glutamate receptor. These results show that the rod and cone inputs to DBCs are mediated by pharmacologically distinct receptors and that subtypes of glutamate receptor existing on single neurones can subserve separate, functionally defined synaptic inputs.     

Genetic linkage between X-chromosome markers and bipolar affective illness

A pedigree study shows close linkage of bipolar affective illness (manic depression) to the X-chromosome markers colour blindness and glucose-6-phosphate dehydrogenase deficiency. The maximum lod score ranges from 7.52 (assuming homogeneity) to 9.17 (assuming heterogeneity); that is, the odds in favour of linkage range between 3 X 10(7) to 1 and 10(9) to 1. These results provide confirmation that a major psychiatric disorder can be caused by a single genetic defect. As a possible first step in characterizing the primary genetic abnormality, this finding may have important implications for the aetiology, nosology, pathophysiology and, possibly, prevention and treatment of bipolar affective disorder. It also provides a means for identifying and characterizing homogeneous populations of patients and may help in clarifying aetiological heterogeneity.     

杉木无性系种子园花粉数量的研究

本研究为福建省洋口林场1966年的杉木嫁接种子园,包括42个无性系,200株母树,面积0.7公顷,母树平均树高8—9米。 依据母树“雄球花”的数量和生长状况,把种子园的母树区分为三类,即“簇生”、“混生”、“单生”,从各类母树中随机抽取3～4株作为样株,统计每株母树的“雄球花”数量和每个“雄球花”的花粉数量。 研究结果表明,每一个小孢子囊花粉粒的数量是3700粒,每一小孢子叶球含有264个小孢子囊,而一个“雄球花”又含有26个小孢子叶球,再估算出一个“雄球花”产生大约2540×10~4粒花粉。根据杉木种子园中一株母树的“雄球花”数量和一个“雄球花”的花粉粒的数量来估算每株树产生花粉粒的数量。在三种类型的母树中,每株树的花粉平均数量为532×10~8粒,估算这个无性系种子园所生产的花粉数量约91540×10~8粒。     

Cyclic GMP increases photocurrent and light sensitivity of retinal cones

Like retinal rods, cone photoreceptors contain cyclic GMP and light-activated phosphodiesterase. The cGMP phosphodiesterase cascade is thought to mediate phototransduction in rods. Biochemical assays of nucleotide content in cone-dominant retinas, however, have failed to demonstrate light-induced changes in cGMP. Changes in cyclic AMP following light exposure have been reported, leading to the suggestion that in cone phototransduction cAMP assumes a role analogous to that played by cGMP in rods. Cyclic GMP introduced from tight-seal pipettes into isolated cones of the larval tiger salamander, Ambystoma tigrinum, rapidly increases light-modulated membrane current more than 10-fold. In cones, as in rods, cGMP also causes an approximately 10-fold increase in photocurrent duration and a 5- to 10-fold increase in light-sensitivity. Cyclic AMP has no effect on cone photocurrents under the same conditions. Because cGMP has similar effects on photocurrent magnitude and kinetics in both rods and cones, we conclude that cGMP plays corresponding roles in transduction in both vertebrate photoreceptor classes.     

Weak acids may act as teratogens by accumulating in the basic milieu of the early mammalian embryo

Among the eleven drugs or chemicals which are well-documented human teratogens, eight (or their main metabolites) are weak acids whereas none is a weak base. Moreover, 23 out of 32 acids tested have been found to be teratogenic in at least one animal species. The acidic property of drugs may therefore be an important determinant of teratogenicity. We demonstrate here that the intracellular pH (pHi) of the mouse and rat embryo is higher than that of maternal plasma, as determined by the relative accumulation of dimethadione. The antiepileptic drug valproic acid and its pharmacologically active unsaturated metabolite accumulate in embryonic tissue to higher concentrations than in maternal plasma, whereas the essentially neutral amide of valproic acid (valpromide) or ethosuximide do not accumulate in the embryo; we further demonstrate in the rat that the pHi of the embryo decreases with advancing gestation; in general agreement with the pH partition hypothesis, the exposure of the embryo to valproic acid also decreases significantly during that period. Furthermore, the amides of two weak acid teratogens, valpromide and methoxyacetamide, and the imide ethosuximide, are much less teratogenic than their acid counterparts. Our results suggest that weakly acidic drugs, by virtue of their physico-chemical nature, accumulate in the early embryo with its relatively high pHi.     

悬铃木化学调控脱果的研究

为了控制悬铃木果毛对城市环境的污染，在悬铃木初花期，用化学药剂处理之后，嫩枝上的球果鲜重减轻，含水量下降，电解质外渗增加，球果活力降低，致使球果皱缩，萎蔫，干枯而脱落，脱果率达９５％以上。研究表明，这与球果内过氧化氢酶活性下降，Ｈ２Ｏ２大量积累，破坏细胞质膜有关。     

Role of visual pigment properties in rod and cone phototransduction

Retinal rods and cones share a phototransduction pathway involving cyclic GMP. Cones are typically 100 times less photosensitive than rods and their response kinetics are several times faster, but the underlying mechanisms remain largely unknown. Almost all proteins involved in phototransduction have distinct rod and cone variants. Differences in properties between rod and cone pigments have been described, such as a 10-fold shorter lifetime of the meta-II state (active conformation) of cone pigment and its higher rate of spontaneous isomerization, but their contributions to the functional differences between rods and cones remain speculative. We have addressed this question by expressing human or salamander red cone pigment in Xenopus rods, and human rod pigment in Xenopus cones. Here we show that rod and cone pigments when present in the same cell produce light responses with identical amplification and kinetics, thereby ruling out any difference in their signalling properties. However, red cone pigment isomerizes spontaneously 10,000 times more frequently than rod pigment. This high spontaneous activity adapts the native cones even in darkness, making them less sensitive and kinetically faster than rods. Nevertheless, additional factors are probably involved in these differences.     

Requirement of TRPC channels in netrin-1-induced chemotropic turning of nerve growth cones

Ion channels formed by the TRP (transient receptor potential) superfamily of proteins act as sensors for temperature, osmolarity, mechanical stress and taste. The growth cones of developing axons are responsible for sensing extracellular guidance factors, many of which trigger Ca2+ influx at the growth cone; however, the identity of the ion channels involved remains to be clarified. Here, we report that TRP-like channel activity exists in the growth cones of cultured Xenopus neurons and can be modulated by exposure to netrin-1 and brain-derived neurotrophic factor, two chemoattractants for axon guidance. Whole-cell recording from growth cones showed that netrin-1 induced a membrane depolarization, part of which remained after all major voltage-dependent channels were blocked. Furthermore, the membrane depolarization was sensitive to blockers of TRP channels. Pharmacological blockade of putative TRP currents or downregulation of Xenopus TRP-1 (xTRPC1) expression with a specific morpholino oligonucleotide abolished the growth-cone turning and Ca2+ elevation induced by a netrin-1 gradient. Thus, TRPC currents reflect early events in the growth cone's detection of some extracellular guidance signals, resulting in membrane depolarization and cytoplasmic Ca2+ elevation that mediates the turning of growth cones.     

杉木种子园结实量近期预测方法的研究

本文用可见半面树冠球果估测法、球果切开法和标准木法对安徽省山斗杉木种子园结实量进行了研究。结果表明,可见半面树冠球果估测法工作量小,精度较高,至少可以提前3个月预测杉木的结实量。把可见半面树冠球果估测法与球果切开法结合使用,可以预测单株或林分的种子潜在产量。     

Re-evaluation of the linkage relationship between chromosome 11p loci and the gene for bipolar affective disorder in the Old Order Amish

Reanalysis of an Old Order Amish pedigree, to include several new individuals and two changes in clinical status, markedly reduces the probability of linkage between bipolar affective disorder and the Harvey-ras-1 oncogene and insulin loci on chromosome 11. This linkage can be excluded using a large lateral extension of the original Amish pedigree.     

金属露天矿生产计划优化算法的改进

针对露天矿生产计划优化中使用锥体排除法产生地质最优开采体序列时，不考虑锥体之间重叠部分对相应锥体的平均品位影响的问题，提出了改进的锥体排除算法.该算法在锥体排除过程中，重新确定了锥体的空间搜索逻辑，同时重新计算锥体数组中受品位最低锥体影响的各锥体的平均品位并重新排序.把新算法产生的地质最优开采体序列作为状态变量建立动态排序模型，对所有可行的路径进行评价，得出NPV最大的路径作为最优开采方案.实例应用表明，在相同技术经济条件下，改进后的优化算法无论是生产能力稳定性还是最终净现值都明显优于原算法，其中NPV提高了105%.     

The spatial arrangement of cones in the primate fovea.

The retinae of Old World primates contain three classes of light-sensitive cone, which exhibit peak absorption in different spectral regions. But how are the different types of cone arranged in the hexagonal mosaic of the fovea? This question has often been answered with artists' impressions, but never with direct measurements. Staining for antibodies specific to the short-wave photopigment has revealed a sparse, semiregular array of cones; but nothing is known about the arrangement of the more numerous long- and middle-wave cones. Are they randomly distributed, with chance aggregations of one type, as Hartridge postulated in these columns nearly 50 years ago? Or do they exhibit a regular alteration, recalling the systematic mosaics seen in some non-mammalian species? Or, conversely, is there positive clumping of particular cone types, as might be expected if local patches of cones were descended from a single precursor cell? We have made direct microspectrophotometric measurements of patches of foveal retina from Old World monkeys, and report here that the distribution of long- and middle-wave cones is locally random. These two cone types are present in almost equal numbers, and not in the ratio of 2:1 that has been postulated for the human fovea.     

Cyclic AMP/GMP-dependent modulation of Ca2+ channels sets the polarity of nerve growth-cone turning

Signalling by intracellular second messengers such as cyclic nucleotides and Ca2+ is known to regulate attractive and repulsive guidance of axons by extracellular factors. However, the mechanism of interaction among these second messengers in determining the polarity of the guidance response is largely unknown. Here, we report that the ratio of cyclic AMP to cyclic GMP activities sets the polarity of netrin-1-induced axon guidance: high ratios favour attraction, whereas low ratios favour repulsion. Whole-cell recordings of Ca2+ currents at Xenopus spinal neuron growth cones indicate that cyclic nucleotide signalling directly modulates the activity of L-type Ca2+ channels (LCCs) in axonal growth cones. Furthermore, cGMP signalling activated by an arachidonate 12-lipoxygenase metabolite suppresses LCC activity triggered by netrin-1, and is required for growth-cone repulsion mediated by the DCC-UNC5 receptor complex. By linking cAMP and cGMP signalling and modulation of Ca2+ channel activity in growth cones, these findings delineate an early membrane-associated event responsible for signal transduction during bi-directional axon guidance.