Coherence between solar activity and the East Asian winter monsoon variability in the past 8000 years from Yangtze River-derived mud in the East China Sea

AMS(14)C dating and grain-size analysis for Core PC-6, located in the middle of a mud area on the inner shelf of the East China Sea (ECS), were used to rebuild the Holocene history of the East Asian winter monsoon (EAWM). The 7.5-m core recorded the history of environmental changes during the postglacial transgression. The core's mud section (the upper 450 cm) has been formed mainly by suspended sediment delivered from the Yangtze River mouth by the ECS Winter Coastal Current (ECSWCC) since 7.6 kyr BP. Using a mathematical method called "grain size vs. standard deviatioW', we can divide the Core PC-6's grain-size distribution into two populations at about 28 mu m. The fine population (< 28 mu m) is considered to be transported by the ECSWCC as suspended loads. Content of the fine population changes little and represents a stable sedimentary environment in accord with the present situation. Thus, variation of mean grain-size from the fine population would reflect the strength of ECSWCC, which is mainly controlled by the East Asian winter monsoon. Abrupt increasing mean grain size in the mud section is inferred to be transported by sudden strengthened ECSWCC, which was caused by the strengthened EAWM. Thus, the high resolution mean grain-size variation might serve as a proxy for reconstruction of the EAWM. A good correlation between sunspot change and the mean grain-size of suspended fine population suggests that one of the primary controls on centennial- to decadal-scale changes of the EAWM in the past 8 ka is the variations of sun irradiance, i.e., the EAWM will increase in intensity when the number of sunspots decreases. Spectral analyses of the mean grain-size time series of Core PC-6 show statistically significant periodicities centering on 2463, 1368, 128, 106, 100, 88-91, 7678, and 70-72 years. The EAWM and the East Asian summer monsoon (EASM) agree with each other well on these cycles, and the East Asian Monsoon (EAM) and the Indian Monsoon also share in concurrent cycles in Holocene, which are in accord with the changes of the sun irradiance. (c) 2005 Elsevier B.V. All rights reserved.

靶向斑马鱼VEGF的shRNA表达载体的构建及其对斑马鱼胚胎血管发育的影响

血管内皮生长因子(vascular endothelial growth factor, VEGF)是一种多功能的细胞因子，其主要作用是促进血管内皮细胞增殖和增加血管通透性，是肿瘤及正常组织血管生成的中心调控因素，以VEGF为靶点的肿瘤血管靶向性治疗成为近几年肿瘤治疗的新途径。RNAi是近年来新发展的一项反向遗传学技术，是一种研究基因功能的有力工具。斑马鱼作为一种重要的模式生物，被广泛用于胚胎的分子发育机制、疾病模型的构建以及药物筛选等研究中。然而在斑马鱼中运用RNAi技术进行基因功能研究是一个相对较新的领域，研究资料较少，并且目前进行的斑马鱼RNAi实验中，siRNA大都是通过化学方法或体外转录合成的。体外合成的siRNA在进入体内后会被降解而无法达到持久阻抑基因表达的目的。因此本研究旨在探讨VEGF特异性siRNA表达载体对斑马鱼VEGF基因的沉默作用，通过分析表型及相关细胞因子的变化，阐明VEGF对斑马鱼胚胎血管生成的影响及作用机制。 研究通过计算机辅助设计软件，针对斑马鱼VEGF mRNA不同位点设计合成了4段含siRNA特异序列的DNA单链，经退火，克隆入pSilencer 4.1-CMV neo载体CMV启动子下游，构建了重组质粒pS1-VEGF、pS2-VEGF、pS3-VEGF及pS4-VEGF。 通过显微注射的方法将载体导入1-2细胞期斑马鱼体内，于胚胎发育的48 h采用RT-PCR的方法检测VEGF基因的表达量，研究不同干扰序列对VEGF基因表达的干涉作用。结果显示，针对不同位点的表达载体对VEGF基因表达的抑制效率有显著差异。它们对VEGF mRNA的抑制率分别为80.5%，42.8%，12.5%，40.7%。通过筛选我们得到了一条具有高效抑制作用的载体pS1-VEGF，该载体的相应序列靶向斑马鱼两个主要异构体VEGF165和VEGF121的共有外显子序列。 形态学检测结果显示，注射了pS1-VEGF的胚胎出现了心包膜水肿、血流速度减慢、循环红细胞堆积等症状。定量碱性磷酸酶染色显示，注射pS1-VEGF能够抑制斑马鱼胚胎新生血管的形成，当注射剂量为0.4 ng时，血管生成的抑制率为31.8%。NBT/BCIP血管染色显示，注射该载体后72 h，50%的斑马鱼肠下静脉、节间血管以及其它血管的发育受到不同程度的抑制。随着注射剂量的加大，血管发育受抑制的情况也随之加重，当注射剂量为1 ng时，只有心脏、头部及卵黄有血液循环。对干扰效果的特异性进行了研究，结果表明pS1-VEGF对斑马鱼内源基因胸苷酸合成酶（thymidylate synthase, TS）基因的表达没有明显的抑制作用。针对TS基因的shRNA表达载体及与斑马鱼没有同源性的对照载体对VEGF基因表达也没有明显的抑制作用。浓度梯度实验表明在0-1.2 ng的范围内干扰效果具有剂量依赖性。 以胚胎整体原位杂交的方法检测质粒对VEGF基因受体NRP1基因表达的影响，发现VEGF特异性shRNA表达载体能够引起NRP1基因表达的降低，说明斑马鱼中VEGF所介导的血管生成作用至少在部分上是依赖于NRP通路所调节的。 本研究工作为进一步研究斑马鱼基因功能、VEGF调控网络提供了一个快速、有效的手段，为阐明斑马鱼的血管生成机制提供了新的资料，为采用RNAi技术，以VEGF为靶点，以斑马鱼为模型对肿瘤进行基因治疗研究奠定了基础。

Response of the diatom flora in Jiaozhou Bay, China to environmental changes during the last century

The diatom flora in a 164 cm long sediment core obtained from Jiaozhou Bay (Yellow Sea, China) was analyzed in order to trace the response of diatoms to environmental changes over the past 100 years. The sediment core was dated by Pb-210 and Cs-137 and represented approximately 100 years (1899-2001 A.D.). The flora was mainly composed of centric diatoms (59-96%). The concentration of diatoms declined sharply above 30 cm (after similar to 1981 A.D.), while the dominant species changed from Thalassiosira anguste-lineatus, Thalassiosira eccentria, Coscinodiscus excentricus, Coscinodiscus concinnus and Diploneis gorjanovici to Cyclotella stylorum and Paralia sulcata. Species richness decreased slightly, and the cell abundance of warm-water species increased. We argue that these floral changes were probably caused by climate change in combination with eutrophication resulting from aquaculture and sewage discharge. (c) 2007 Elsevier B.V. All rights reserved.

Elemental carbon record of paleofire history on the Chinese Loess Plateau during the last 420 ka and its response to environmental and climate changes

An elemental carbon (EC) record, covering the last 420 ka, was reconstructed using chemical oxidation method on a loess and paleosol sequence from the Lingtai section on the Chinese Loess Plateau. The EC record reveals the paleofire history and its relationship with climate and vegetation changes on the Chinese Loess Plateau. Our results show that the EC abundance is generally higher in the paleosols than in the loess layers, showing a glacial/interglacial pattern, which is coincident with biomass changes. This variation pattern indicates that paleofires were intensified when biomass accumulated and climate changed abruptly especially from wet to dry conditions. The EC abundance increases sharply at similar to 130 kaB.P., indicating a dramatic change in the vegetation and climate variation patterns. The occurrence of a peak value with the highest average EC abundance in the Holocene may reflect the occurrence of a major climate event at similar to 6 kaB.P., and may also be partly due to more frequent anthropogenic fire usages. (c) 2007 Elsevier B.V. All rights reserved.

北天山新生代构造演化与古环境演变

The Tianshan Mountains is located about 1000-2000 km north of the India-Asia suture and is the most outstanding topography in central Asia, with transmeridional length of nearly 2500 km, north-southern wideness of ~ 300-500 km, peaks exceeding 7000 m above sea level (asl.), and average altitude of over 4000 m asl. Much of the modern relief of the Tianshan Range is a result of contraction driven by the collision of the India subcontinent with the southern margin of Asia, which began in early Tertiary and continues today. Understanding where, when and how the deformation of the Tianshan Mountains occurred is essential to decipher the mechanism of intracontinental tectonics, the process of foreland basin evolution and mountain building, and the history of climate change in central Asia. In order to better constrain the Cenozoic building history of the Tianshan Mountains and the climate change in the southern margin of the Junggar Basin, we carried out multiple studies of magnetostratigraphy, sedimentology, and stable isotopes of paleosol carbonate at the Jingou River section, which is located at the Huoerguosi anticline, the westernest one of the second folds and thrust faults zone in the northern piedmont of the Tianshan Mountains. The Jingou River section with a thickness of about 4160 m is continuous in deposits according to the observed gradual change in sedimentary environments and can be divided into five formations: Anjihaihe, Shawan, Taxihe, Dushanzi and Xiyu in upward sequence. Characteristic remamences were isolated by progressive thermal demagnetization, generally between 300 and 680℃. A total of 1133 out of 1607 samples yielded well-defined ChRMs and were used to establish the magnetostratigraphic column of a 3270-m-thick section from the exposed base of the Anjihaihe Formation to the middle of the Xiyu Formation. Two vertebrate fossil sites and a good correlation with the CK95 geomagnetic polarity time scale suggest that the section was deposited from ~30.5 to ~4.6 Ma and the age of the top of the Xiyu formation is ~2.6 Ma based on an extrapolation of the sedimentation rates. A plot of magnetostratigraphic age vs. height at the Jingou River section shows that significant increases in sedimentation rates as well as notable changes in depositional environments occurred at ~26-22.5 Ma, ~13-11 Ma and ~7 Ma, which represent the initial uplift of the Tianshan Mountains and two subsequent rapid uplift events. In addition, changes in sedimentation rates display characteristic alternations between increases and decreases, which probably indicate that the uplift of the Tianshan Mountains was episodic. We discussed the history of C4 biomass and climatic conditions in the southern margin of the Junggur Basin using the stable carbon and oxygen isotope composition of paleosol carbonates from the Jingou River section during ~17.5-6.5 Ma. The δ13C values indicate that the proportion of C4 biomass was uniform and moderate (15-20 %) during the interval of ~17.5-6.5 Ma. We proposed three hypotheses for this pattern of C4 biomass: (1) counteraction of two opposed factors (global cooling since ~15 Ma and thereafter increased dry and seasonality in central Asia) controlling the growth of C4 grasses, (2) variability in abundance of C3 grasses relative to C3 trees and shrubs if vegetation had ever changed in ecosystems, and (3) the higher latitude of the studied region. The δ18O values show a stepwise negative trend since ~13 Ma which may be attributed to three factors: (1) the temperature decreasing gradually after the middle Miocene (~15 Ma), (2) the increasing contribution of the moistures carried by the polar air masses from the Arctic Ocean to precipitation, and (3) the gradual retreat westward and disappearance of the Paratethys Ocean. Among them, which one played a more important role will need further study of the paleoclimate in central Asia.

北山及邻区古生代-早中生代增生与碰撞大地构造格局

The Beishan orogenic collage locates at the triple-joint among Xinjiang, Gansu, and Inner Mongolia Provinces, at which the Siberian, Tarim and North China plates join together. It also occupies the central segment of the southern Central Asian Orogenic Belt (CAOB). The main study area in the present suty focused on the southwest part of the Beishan Mountain, which can be subdivided into four units southernward, the Mazhongshan continental block, Huaniushan Arc, Liuyuan suture zone and Shibanshan-Daqishan Arc. 1. The Huaniushan Arc was formed by northernward dipping subduction from the Orcovician to Permian, in which volcanic rocks ranging from basic to acidic with island arc affinity were widely developed. The granitiod intrusions become smaller and younger southward, whichs indicates a southward rollback of slab. The granitiod intrusions are mainly composed of I type granites, and their geochemical compositions suggest that they have affinities of island arc settings. In the early Paleozoic（440Ma-390Ma）. The Shibanshan-Daqishan Arc, however, were produced in the southernward dipping subduction system from Carboniferous to Permian. Volcanic rocks from basic to acidic rocks are typical calcic-alkaline rocks. The granitiod intrusions become smaller and younger northernward, indicating subdution with a northernward rollback. The granitiod intrusions mainly consist of I-type granites, of which geochemical data support they belong to island arc granite. 2. Two series of adakite intrusions and eruptive rocks have been discovered in the southern margin of the Huaniushan Island Arc. The older series formed during Silurian (441.7±2.5Ma) are gneiss granitoid. These adakite granites intruded the early Paleozoic Liuyuan accretionary complex, and have the same age as most of the granite intrusions in the Huanniushan Arc. Their geochemical compostions demonstrate that they were derived from partial melting of the subudcted oceanic slab. These characteristics indicate a young oceanic crust subduction in the early Paleozoic. The late stage adakites with compositons of dacites associate with Nb-enriched basalts, and island arc basalts and dacites. Their geochemistries demonstrate that the adakites are the products of subducted slab melts, whereas the Nb-enriched basalt is products of the mantle wedge which have metasomatized by adakite melts. Such a association indicates the existences of a young ocean slab subduction. 3. The Liuyuan suture zone is composed of late Paleozoic ophiolites and two series of accretionary complexes with age of early Paleozoic. The early Paleozoic accretionary complex extensively intruded by early Palozioc granites is composed of metamorphic clastics, marble, flysch, various metamorphic igneous rocks (ultramafic, mafic and dacite), and eclogite blocks, which are connected by faults. The original compositions of the rocks in this complex are highly varied, including MORB, E-MORB, arc rocks. Geochronological study indicates that they were formed during the Silurian (420.9±2.5Ma and 421.1±4.3Ma). Large-scale granitiods intruded in the accretionary complex suggest a fast growth effect at the south margin of the Huaniushan arc. During late Paleozoic, island arc were developed on this accretionary complex. The late Paleozoic ophiolite has an age of early Permian (285.7±2.2Ma), in which the rock assemblage includes ultra-mafic, gabbros, gabbros veins, massive basalts, pillow basalt, basaltic clastic breccias, and thin layer tuff, with chert on the top.These igneous rocks have both arc and MORB affinities, indicating their belonging to SSZ type ophiolite. Therefore, oceanic basins area were still existed in the Liuyuan area in the early Permian. 4. The mafic-ultramafic complexes are distributed along major faults, and composed of zoned cumulate rocks, in which peridotites are surrounded by pyroxenite, hornblendites, gabbros norite and diorite outward. They have island-arc affinities and are consistent with typical Alaska-type mafic-ultramafic complexes. The geochronological results indicate that they were formed in the early Permian. 5. The Liuyuan A-type granite were formed under post-collisional settings during the late Triassic (230.9±2.5Ma), indicating the persistence of orogenic process till the late Triassic in the study area. Geochronological results suggested that A-type granites become younger southward from the Wulungu A-type granite belt to Liuyuan A-type granite belt, which is in good agreement with the accretionary direction of the CAOB in this area, which indicate that the Liuyuan suture is the final sture of the Paleo-Asin Ocean. 6. Structural geological evidence demonstrate the W-E spreading of main tectonic terrenes. These terrenes had mainly underwent through S-N direction contraction and NE strike-faulting. The study area had experienced a S-N direction compression after the Permian, indicating a collisional event after the Permian. Based on the evidene from sedimentary geology, paleontology, and geomagnetism, our studies indicate that the orogenic process can be subdivided into five stages: (1) the pre-orogenic stage occurred before the Ordovicain; (2) the subduction orogenic stage occurred from the Orcovician to the Permian; (3) the collisional orogenic stage occurred from the late Permian to the late Triassic; (4) the post-collision stage occurred after the Triassic. The Liuyuan areas have a long and complex tectonic evolutional history, and the Liuyuan suture zone is one of the most important sutures. It is the finally suture zone of the paleo-Asian ocean in the Beishan area.

碳、氧稳定同位素分析在古环境研究中的应用

A number of proxy records of paleoenvironment using stable isotopes could show the history of past environmental changes. These archives include peat and lake sediments, loess-paleosot sequence, fossil mammals and stalagmite, and so on. The stable isotopic composition of carbonate and organic matter and frequency magnetic susceptibility from Tianshuigou and Yuanlei loess-palesol sequence can be used to give estimates of the paleoenvironmental history of Dali, and even of the whole Chinese Loess Plateau during the last 250ka. Features of the High Temperature and Large Precipitation Event in the Tibet Plateau and its adjacent area during 40~30kaBP had been studied by Professor Shi Y. In this dissertation, its impact on Chinese Loess Plateau has been discussed again. Carbon and oxygen isotopic ratios, magnetic susceptibility and frequency magnetic susceptibility in Tianshuigou and Yuanlei profiles show that the Event in this area is not so stronger as the Tibet Plateau. The carbon isotopic composition of organic matter in Tianshuigou, Yuanlei, dingcun and Jingcun loess-palesol sequences are indicative of major changes in the paleovagetation between terrace and plain of the Chinese Loess Plateau. Water is one of the most important factors adjusting the relative biomass of C4 plant in terrestrial ecosystems. Stable carbon isotope ratio of vertebrate tooth enamel is used increasingly to reconstruct environmental and ecological information modern and ancient ecosystems. The SI3C value of tooth enamel bioapatites can distinguish between browsers and grazers. Data from typical grassland of Inter Mongolia, the Alpine meadow of Qinghai-Tibet Plateau and the Yaluzangbu Great Canyon indicate that diets of mammals could record the relative biomass of C4 plant only in the C4 dominated ecosystem. In a C3 dominated ecosystem, diet of mammals would include more C3 plants than vegetation. According to Professor Cerling, proxy records from North and South America, Africa and Pakistan show that at the end of the Miocene (between 8Ma to 6 Ma) there was a global expansion of CA biomass, probably when atmospheric CO2 levels declined. Thus, "C4 world" and "CO2 starvation" are put forward. In this dissertation, carbon isotopes of fossil tooth such as Equus sanmeniensis and Hipparion chiai from Linxia, China reveal that there is a C3 dominated ecosystem in the late Miocene. Diets of ancient mammals in Linxia are not evidence of global expansion of C4 biomass.

Shh/Boc signaling is required for sustained generation of ipsilateral projecting ganglion cells in the mouse retina

Sonic Hedgehog (Shh) signaling is an important determinant of vertebrate retinal ganglion cell (RGC) development. In mice, there are two major RGC populations: (1) the Islet2-expressing contralateral projecting (c)RGCs, which both produce and respond to Shh; and (2) the Zic2-expressing ipsilateral projecting RGCs (iRGCs), which lack Shh expression. In contrast to cRGCs, iRGCs, which are generated in the ventrotemporal crescent (VTC) of the retina, specifically express Boc, a cell adhesion molecule that acts as a high-affinity receptor for Shh. In Boc −/− mutant mice, the ipsilateral projection is significantly decreased. Here, we demonstrate that this phenotype results, at least in part, from the misspecification of a proportion of iRGCs. In Boc−/− VTC, the number of Zic2-positive RGCs is reduced, whereas more Islet2/Shh-positive RGCs are observed, a phenotype also detected in Zic2 and Foxd1 null embryos.

3'-UTR SIRF: A database for identifying clusters of short interspersed repeats in 3' untranslated regions

BACKGROUND:Short (~5 nucleotides) interspersed repeats regulate several aspects of post-transcriptional gene expression. Previously we developed an algorithm (REPFIND) that assigns P-values to all repeated motifs in a given nucleic acid sequence and reliably identifies clusters of short CAC-containing motifs required for mRNA localization in Xenopus oocytes.DESCRIPTION:In order to facilitate the identification of genes possessing clusters of repeats that regulate post-transcriptional aspects of gene expression in mammalian genes, we used REPFIND to create a database of all repeated motifs in the 3' untranslated regions (UTR) of genes from the Mammalian Gene Collection (MGC). The MGC database includes seven vertebrate species: human, cow, rat, mouse and three non-mammalian vertebrate species. A web-based application was developed to search this database of repeated motifs to generate species-specific lists of genes containing specific classes of repeats in their 3'-UTRs. This computational tool is called 3'-UTR SIRF (Short Interspersed Repeat Finder), and it reveals that hundreds of human genes contain an abundance of short CAC-rich and CAG-rich repeats in their 3'-UTRs that are similar to those found in mRNAs localized to the neurites of neurons. We tested four candidate mRNAs for localization in rat hippocampal neurons by in situ hybridization. Our results show that two candidate CAC-rich (Syntaxin 1B and Tubulin beta4) and two candidate CAG-rich (Sec61alpha and Syntaxin 1A) mRNAs are localized to distal neurites, whereas two control mRNAs lacking repeated motifs in their 3'-UTR remain primarily in the cell body.CONCLUSION:Computational data generated with 3'-UTR SIRF indicate that hundreds of mammalian genes have an abundance of short CA-containing motifs that may direct mRNA localization in neurons. In situ hybridization shows that four candidate mRNAs are localized to distal neurites of cultured hippocampal neurons. These data suggest that short CA-containing motifs may be part of a widely utilized genetic code that regulates mRNA localization in vertebrate cells. The use of 3'-UTR SIRF to search for new classes of motifs that regulate other aspects of gene expression should yield important information in future studies addressing cis-regulatory information located in 3'-UTRs.

Neural Control of Interlimb Coordination and Gait Timing in Bipeds and Quadrupeds

1) A large body of behavioral data conceming animal and human gaits and gait transitions is simulated as emergent properties of a central pattern generator (CPG) model. The CPG model incorporates neurons obeying Hodgkin-Huxley type dynamics that interact via an on-center off-surround anatomy whose excitatory signals operate on a faster time scale than their inhibitory signals. A descending cornmand or arousal signal called a GO signal activates the gaits and controL their transitions. The GO signal and the CPG model are compared with neural data from globus pallidus and spinal cord, among other brain structures. 2) Data from human bimanual finger coordination tasks are simulated in which anti-phase oscillations at low frequencies spontaneously switch to in-phase oscillations at high frequencies, in-phase oscillations can be performed both at low and high frequencies, phase fluctuations occur at the anti-phase in-phase transition, and a "seagull effect" of larger errors occurs at intermediate phases. When driven by environmental patterns with intermediate phase relationships, the model's output exhibits a tendency to slip toward purely in-phase and anti-phase relationships as observed in humans subjects. 3) Quadruped vertebrate gaits, including the amble, the walk, all three pairwise gaits (trot, pace, and gallop) and the pronk are simulated. Rapid gait transitions are simulated in the order--walk, trot, pace, and gallop--that occurs in the cat, along with the observed increase in oscillation frequency. 4) Precise control of quadruped gait switching is achieved in the model by using GO-dependent modulation of the model's inhibitory interactions. This generates a different functional connectivity in a single CPG at different arousal levels. Such task-specific modulation of functional connectivity in neural pattern generators has been experimentally reported in invertebrates. Phase-dependent modulation of reflex gain has been observed in cats. A role for state-dependent modulation is herein predicted to occur in vertebrates for precise control of phase transitions from one gait to another. 5) The primary human gaits (the walk and the run) and elephant gaits (the amble and the walk) are sirnulated. Although these two gaits are qualitatively different, they both have the same limb order and may exhibit oscillation frequencies that overlap. The CPG model simulates the walk and the run by generating oscillations which exhibit the same phase relationships. but qualitatively different waveform shapes, at different GO signal levels. The fraction of each cycle that activity is above threshold quantitatively distinguishes the two gaits, much as the duty cycles of the feet are longer in the walk than in the run. 6) A key model properly concerns the ability of a single model CPG, that obeys a fixed set of opponent processing equations to generate both in-phase and anti-phase oscillations at different arousal levels. Phase transitions from either in-phase to anti-phase oscillations, or from anti-phase to in-phase oscillations, can occur in different parameter ranges, as the GO signal increases.

Simulations of X and Y Retinal Ganglion Cell Behavior with a Nonlinear Push-pull Model of Spatiotemporal Retinal Processing

This article describes a nonlinear model of neural processing in the vertebrate retina, comprising model photoreceptors, model push-pull bipolar cells, and model ganglion cells. Previous analyses and simulations have shown that with a choice of parameters that mimics beta cells, the model exhibits X-like linear spatial summation (null response to contrast-reversed gratings) in spite of photoreceptor nonlinearities; on the other hand, a choice of parameters that mimics alpha cells leads to Y-like frequency doubling. This article extends the previous work by showing that the model can replicate qualitatively many of the original findings on X and Y cells with a fixed choice of parameters. The results generally support the hypothesis that X and Y cells can be seen as functional variants of a single neural circuit. The model also suggests that both depolarizing and hyperpolarizing bipolar cells converge onto both ON and OFF ganglion cell types. The push-pull connectivity enables ganglion cells to remain sensitive to deviations about the mean output level of nonlinear photoreceptors. These and other properties of the push-pull model are discussed in the general context of retinal processing of spatiotemporal luminance patterns.

A Unified Model of Spatiotemporal Processing in the Retina

A computational model of visual processing in the vertebrate retina provides a unified explanation of a range of data previously treated by disparate models. Three results are reported here: the model proposes a functional explanation for the primary feed-forward retinal circuit found in vertebrate retinae, it shows how this retinal circuit combines nonlinear adaptation with the desirable properties of linear processing, and it accounts for the origin of parallel transient (nonlinear) and sustained (linear) visual processing streams as simple variants of the same retinal circuit. The retina, owing to its accessibility and to its fundamental role in the initial transduction of light into neural signals, is among the most extensively studied neural structures in the nervous system. Since the pioneering anatomical work by Ramón y Cajal at the turn of the last century[1], technological advances have abetted detailed descriptions of the physiological, pharmacological, and functional properties of many types of retinal cells. However, the relationship between structure and function in the retina is still poorly understood. This article outlines a computational model developed to address fundamental constraints of biological visual systems. Neurons that process nonnegative input signals-such as retinal illuminance-are subject to an inescapable tradeoff between accurate processing in the spatial and temporal domains. Accurate processing in both domains can be achieved with a model that combines nonlinear mechanisms for temporal and spatial adaptation within three layers of feed-forward processing. The resulting architecture is structurally similar to the feed-forward retinal circuit connecting photoreceptors to retinal ganglion cells through bipolar cells. This similarity suggests that the three-layer structure observed in all vertebrate retinae[2] is a required minimal anatomy for accurate spatiotemporal visual processing. This hypothesis is supported through computer simulations showing that the model's output layer accounts for many properties of retinal ganglion cells[3],[4],[5],[6]. Moreover, the model shows how the retina can extend its dynamic range through nonlinear adaptation while exhibiting seemingly linear behavior in response to a variety of spatiotemporal input stimuli. This property is the basis for the prediction that the same retinal circuit can account for both sustained (X) and transient (Y) cat ganglion cells[7] by simple morphological changes. The ability to generate distinct functional behaviors by simple changes in cell morphology suggests that different functional pathways originating in the retina may have evolved from a unified anatomy designed to cope with the constraints of low-level biological vision.

Barnacle cement: a polymerization model based on evolutionary concepts.

Enzymes and biochemical mechanisms essential to survival are under extreme selective pressure and are highly conserved through evolutionary time. We applied this evolutionary concept to barnacle cement polymerization, a process critical to barnacle fitness that involves aggregation and cross-linking of proteins. The biochemical mechanisms of cement polymerization remain largely unknown. We hypothesized that this process is biochemically similar to blood clotting, a critical physiological response that is also based on aggregation and cross-linking of proteins. Like key elements of vertebrate and invertebrate blood clotting, barnacle cement polymerization was shown to involve proteolytic activation of enzymes and structural precursors, transglutaminase cross-linking and assembly of fibrous proteins. Proteolytic activation of structural proteins maximizes the potential for bonding interactions with other proteins and with the surface. Transglutaminase cross-linking reinforces cement integrity. Remarkably, epitopes and sequences homologous to bovine trypsin and human transglutaminase were identified in barnacle cement with tandem mass spectrometry and/or western blotting. Akin to blood clotting, the peptides generated during proteolytic activation functioned as signal molecules, linking a molecular level event (protein aggregation) to a behavioral response (barnacle larval settlement). Our results draw attention to a highly conserved protein polymerization mechanism and shed light on a long-standing biochemical puzzle. We suggest that barnacle cement polymerization is a specialized form of wound healing. The polymerization mechanism common between barnacle cement and blood may be a theme for many marine animal glues.

Emi2-mediated inhibition of E2-substrate ubiquitin transfer by the anaphase-promoting complex/cyclosome through a D-box-independent mechanism.

Vertebrate eggs are arrested at Metaphase II by Emi2, the meiotic anaphase-promoting complex/cyclosome (APC/C) inhibitor. Although the importance of Emi2 during oocyte maturation has been widely recognized and its regulation extensively studied, its mechanism of action remained elusive. Many APC/C inhibitors have been reported to act as pseudosubstrates, inhibiting the APC/C by preventing substrate binding. Here we show that a previously identified zinc-binding region is critical for the function of Emi2, whereas the D-box is largely dispensable. We further demonstrate that instead of acting through a "pseudosubstrate" mechanism as previously hypothesized, Emi2 can inhibit Cdc20-dependent activation of the APC/C substoichiometrically, blocking ubiquitin transfer from the ubiquitin-charged E2 to the substrate. These findings provide a novel mechanism of APC/C inhibition wherein the final step of ubiquitin transfer is targeted and raise the interesting possibility that APC/C is inhibited by Emi2 in a catalytic manner.

Cytokinesis proteins Tum and Pav have a nuclear role in Wnt regulation.

Wg/Wnt signals specify cell fates in both invertebrate and vertebrate embryos and maintain stem-cell populations in many adult tissues. Deregulation of the Wnt pathway can transform cells to a proliferative fate, leading to cancer. We have discovered that two Drosophila proteins that are crucial for cytokinesis have a second, largely independent, role in restricting activity of the Wnt pathway. The fly homolog of RacGAP1, Tumbleweed (Tum)/RacGAP50C, and its binding partner, the kinesin-like protein Pavarotti (Pav), negatively regulate Wnt activity in fly embryos and in cultured mammalian cells. Unlike many known regulators of the Wnt pathway, these molecules do not affect stabilization of Arm/beta-catenin (betacat), the principal effector molecule in Wnt signal transduction. Rather, they appear to act downstream of betacat stabilization to control target-gene transcription. Both Tum and Pav accumulate in the nuclei of interphase cells, a location that is spatially distinct from their cleavage-furrow localization during cytokinesis. We show that this nuclear localization is essential for their role in Wnt regulation. Thus, we have identified two modulators of the Wnt pathway that have shared functions in cell division, which hints at a possible link between cytokinesis and Wnt activity during tumorigenesis.