Horizontal cells reveal cone type-specific adaptation in primate retina

The human cone visual system maintains contrast sensitivity over a wide range of ambient illumination, a property known as light adaptation. The first stage in light adaptation is believed to take place at the first neural step in vision, within the long, middle, and short wavelength sensitive cone photoreceptors. To determine the properties of adaptation in primate outer retina, we measured cone signals in second-order interneurons, the horizontal cells, of the macaque monkey. Horizontal cells provide a unique site for studying early adaptational mechanisms; they are but one synapse away from the photoreceptors, and each horizontal cell receives excitatory inputs from many cones. Light adaptation occurred over the entire range of light levels evaluated, a luminance range of 15–1,850 trolands. Adaptation was demonstrated to be independent in each cone type and to be spatially restricted. Thus, in primates, a major source of sensitivity regulation occurs before summation of cone signals in the horizontal cell.

Unusual horizontal transfer of a long interspersed nuclear element between distant vertebrate classes

We have shown previously by Southern blot analysis that Bov-B long interspersed nuclear elements (LINEs) are present in different Viperidae snake species. To address the question as to whether Bov-B LINEs really have been transmitted horizontally between vertebrate classes, the analysis has been extended to a larger number of vertebrate, invertebrate, and plant species. In this paper, the evolutionary origin of Bov-B LINEs is shown unequivocally to be in Squamata. The previously proposed horizontal transfer of Bov-B LINEs in vertebrates has been confirmed by their discontinuous phylogenetic distribution in Squamata (Serpentes and two lizard infra-orders) as well as in Ruminantia, by the high level of nucleotide identity, and by their phylogenetic relationships. The horizontal transfer of Bov-B LINEs from Squamata to the ancestor of Ruminantia is evident from the genetic distances and discontinuous phylogenetic distribution. The ancestor of Colubroidea snakes is a possible donor of Bov-B LINEs to Ruminantia. The timing of horizontal transfer has been estimated from the distribution of Bov-B LINEs in Ruminantia and the fossil data of Ruminantia to be 40–50 My ago. The phylogenetic relationships of Bov-B LINEs from the various Squamata species agrees with that of the species phylogeny, suggesting that Bov-B LINEs have been maintained stably by vertical transmission since the origin of Squamata in the Mesozoic era.

Horizontal transfer of oncogenes by uptake of apoptotic bodies

Tumor formation involves the accumulation of a series of genetic alterations that are required for malignant growth. In most malignancies, genetic changes can be observed at the chromosomal level as losses or gains of whole or large portions of chromosomes. Here we provide evidence that tumor DNA may be horizontally transferred by the uptake of apoptotic bodies. Phagocytosis of apoptotic bodies derived from H-rasV12- and human c-myc-transfected rat fibroblasts resulted in loss of contact inhibition in vitro and a tumorigenic phenotype in vivo. Fluorescence in situ hybridization analysis revealed the presence of rat chromosomes or of rat and mouse fusion chromosomes in the nuclei of the recipient murine cells. The transferred DNA was propagated, provided that the transferred DNA conferred a selective advantage to the cell and that the phagocytotic host cell was p53-negative. These results suggest that lateral transfer of DNA between eukaryotic cells may result in aneuploidy and the accumulation of genetic changes that are necessary for tumor formation.

Two recombination-dependent DNA replication pathways of bacteriophage T4, and their roles in mutagenesis and horizontal gene transfer

Two major pathways of recombination-dependent DNA replication, “join-copy” and “join-cut-copy,” can be distinguished in phage T4: join-copy requires only early and middle genes, but two late proteins, endonuclease VII and terminase, are uniquely important in the join-cut-copy pathway. In wild-type T4, timing of these pathways is integrated with the developmental program and related to transcription and packaging of DNA. In primase mutants, which are defective in origin-dependent lagging-strand DNA synthesis, the late pathway can bypass the lack of primers for lagging-strand DNA synthesis. The exquisitely regulated synthesis of endo VII, and of two proteins from its gene, explains the delay of recombination-dependent DNA replication in primase (as well as topoisomerase) mutants, and the temperature-dependence of the delay. Other proteins (e.g., the single-stranded DNA binding protein and the products of genes 46 and 47) are important in all recombination pathways, but they interact differently with other proteins in different pathways. These homologous recombination pathways contribute to evolution because they facilitate acquisition of any foreign DNA with limited sequence homology during horizontal gene transfer, without requiring transposition or site-specific recombination functions. Partial heteroduplex repair can generate what appears to be multiple mutations from a single recombinational intermediate. The resulting sequence divergence generates barriers to formation of viable recombinants. The multiple sequence changes can also lead to erroneous estimates in phylogenetic analyses.

A circadian clock regulates rod and cone input to fish retinal cone horizontal cells.

In the vertebrate retina, the light responses of post-receptor neurons depend on the ambient or background illumination. Using intracellular recording, we have found that a circadian clock regulates the light responses of dark-adapted fish cone horizontal cells. Goldfish were maintained on a 12-hr light/12-hr dark cycle. At different times of the day or night, retinas were superfused in darkness for 90 min ("prolonged darkness"), following which horizontal cells were impaled without the aid of any light flashes. In some of the experiments, fish were kept in constant darkness for 3-48 hr prior to surgery. After prolonged darkness during the night, but not during the day, the light responses of L-type cone horizontal cells resembled those of rod horizontal cells with respect to threshold, waveform, intensity-response functions, and spectral sensitivity. Following light sensitization during the night and day, the light responses of rod and cone horizontal cells were clearly different with respect to threshold, waveform, intensity-response functions, and spectral sensitivity. Under conditions of constant darkness for two full light/dark cycles, average responses of cone horizontal cells to a bright light stimulus during the subjective day were greater than during the subjective night. Prior reversal of the light/dark cycle reversed the 24-hr rhythm of cone horizontal cell responses to bright lights. In addition, following one full cycle of constant darkness, average cone horizontal cell spectral sensitivity during the subjective night closely matched that of rod horizontal cells, whereas average cone horizontal cell spectral sensitivity during the subjective day was similar to that of red (625 nm) cones. These results indicate that the effects of dark adaptation depend on the time of day and are regulated by a circadian clock so that cone input to cone horizontal cells predominates in the day and rod input predominates in the night.

Low-calcium-induced enhancement of chemical synaptic transmission from photoreceptors to horizontal cells in the vertebrate retina.

According to the classical calcium hypothesis of synaptic transmission, the release of neurotransmitter from presynaptic terminals occurs through an exocytotic process triggered by depolarization-induced presynaptic calcium influx. However, evidence has been accumulating in the last two decades indicating that, in many preparations, synaptic transmitter release can persist or even increase when calcium is omitted from the perfusing saline, leading to the notion of a "calcium-independent release" mechanism. Our study shows that the enhancement of synaptic transmission between photoreceptors and horizontal cells of the vertebrate retina induced by low-calcium media is caused by an increase of calcium influx into presynaptic terminals. This paradoxical effect is accounted for by modifications of surface potential on the photoreceptor membrane. Since lowering extracellular calcium concentration may likewise enhance calcium influx into other nerve cells, other experimental observations of "calcium-independent" release may be reaccommodated within the framework of the classical calcium hypothesis without invoking unconventional processes.

Feedback from luminosity horizontal cells mediates depolarizing responses of chromaticity horizontal cells in the Xenopus retina.

It has been proposed that the depolarizing responses of chromaticity horizontal cells (C-HCs) to red light depend on a feedback signal from luminosity horizontal cells (L-HCs) to short-wavelength-sensitive cones in the retinas of lower vertebrates. In this regard we studied the C-HCs of the Xenopus retina. C-HCs and L-HCs were identified by physiological criteria and then injected with neurobiotin. The retina then was incubated with peanut agglutinin, which stains red-but not blue-sensitive cones. Electron microscopic examination revealed that L-HCs contact all cone classes, whereas C-HCs contact only blue-sensitive cones. Simultaneous recordings from C-HC/L-HC pairs established that when the L-HC was saturated by a steady bright red light, C-HCs alone responded to a superimposed blue stimulus. In response to red test flashes, the C-HC response was delayed by approximately 30 msec with respect to the L-HC response. Isolated HCs of both subtypes were examined by whole-cell patch clamp. Both responded to kainate with sustained inward currents and to quisqualate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) with desensitizing currents from a negative holding potential; i.e., both have AMPA-type glutamate receptors. gamma-Aminobutyric acid or glycine opened a chloride channel in the L-HC, whereas the C-HC was unresponsive to either inhibitory amino acid. Since glycine has been shown to abolish selectively the depolarizing response of the C-HC, this finding and other pharmacological data strongly implicate the L-HC in the underlying circuit. Moreover, because the C-HC does not respond to gamma-aminobutyric acid, the neurotransmitter of the L-HC, by elimination, a feedback synapse from L-HC to blue cone is the most plausible mechanism for the creation of depolarizing responses in C-HCs.

Tratamento de esgoto sanitário em reator anaeróbio horizontal de leito fixo (RAHLF): escala piloto

Este trabalho apresenta as avaliações de desempenho, das demandas operacionais e dos fatores intervenientes no aumento da escala da unidade piloto do Reator anaeróbio Horizontal de Leito Fixo (RAHLF) no tratamento de esgoto sanitário após passagem por peneira com malha de 1 mm, durante dois anos de operação. O reator dispunha de volume total de 237,5 1, construídos com tubos comerciais de PVC de 14,5 cm de diâmetro (D), dispostos em cinco módulos horizontais em série de 2,88 m, perfazendo um comprimento total de (L) de 14,4 m e relação de total de L/D de 100. O suporte de imobilização de biomassa, espuma de poliuretano em matrizes cúbicas de 1 cm de aresta, mostrou-se adequado ao desenvolvimento do biofilme. Em partida, sem inoculação prévia, ocorreu a sua consolidação a partir de 70 dias, com predominância de morfologia semelhante a Methanosaeta sp. em relação a da Methanosarcina. Em torno de 90 dias com afluente de 350 mg/l de DQO, observe-se a melhor qualidade do efluente, com valor de 100 mg/l de DQO. Em longa operação ocorreu queda de rendimento e menor reprodutibilidade das previsões do projeto, atribuída aos constantes entupimentos e ineficácia das operações de limpeza, com o comprometimento de volume reacional verificados por estudos de hidrodinâmica. Da investigação das origens dos equipamentos observou-se tratar mais de um efeito local e qualitativamente relacionado à biomassa retida que propriamente quantitativo e extensivo ao longo de todo reator, com produção continuada de polímeros extracelulares, promovendo um efeito sinérgico com os predominantes organismos filamentosos e com os sólidos particulados retidos no leito. Diante das potencialidades desta configuração de reator apontam-se alternativas de mitigação dos entupimentos e o direcionamento dos estudos necessários para novo aumento de escala para o tratamento de esgoto sanitário.

Horizontal Innovation and Interface Patents

Scholars understandably devote a great deal of effort to studying how well patent law works to incentive the most important inventions. After all, these inventions form the foundation of our new technological age. But very little time is spent focusing on the other end of the spectrum, inventions that are no better than what the public already has. At first blush, studying such “horizontal” innovation seems pointless. But this inquiry actually reveals much about how patents can be used in unintended, and arguably, anticompetitive ways. This issue has roots in one unintuitive aspect of patent law. Despite the law’s goal of promoting innovation, patents can be obtained on inventions that are no better than existing technology. Such patents might appear worthless, but companies regularly obtain these patents to cover interfaces. That is because interface patents actually derive value from two distinct characteristics. First, they can have “innovation value” that is based on how much better the patentedinterface is than existing technology. Second, interface patents can also have “compatibility value.” In other words, the patented technology is often essential to make products operate (i.e. compatible) with a particular interface. In practical terms, this means that an interface patent that covers little or no meaningful advance can give a company the ability to extract rents and foreclose competition. This undesirable result is a consequence of how patent law has structured its remedies. For years patent law has implicitly awarded both innovation and compatibility values. Recently, the courts have taken a sensible first step and excluded compatibility value from reasonable royalty recoveries for standard essential patents. This Article argues that the law needs to go further and do the same for all essential interface patents. Additionally, patent law should reform the way it awards injunctions and lost profits to also exclude compatibility value. This proposal has two benefits. It would eliminate the incentives for wasteful patents on horizontal technology. Second, and more importantly, the value of all interfacepatents would be better aligned with the goals of the patent system.

Candidate Conservation Agreements to Minimize Military Conflicts with Wildlife Laws: The Gopher Tortoise (Gopherus polyphemus)

The proposed Endangered Species Act listing of the gopher tortoise has the potential to impact the military mission at installations in the southeastern United States. Candidate Conservation Agreements with the U.S. Fish and Wildlife Service could be a tool to promote conservation and potentially preclude listing. This project identified military activities that could be affected and determined that military natural resources managers are unsure if such an agreement would prevent impacts to the military mission or impose the same restrictions as federal listing. This project found that if a gopher tortoise Candidate Conservation Agreement can be developed such that it benefits the species as well as the military, it should be used as a model for other species.

Agreements with Mr. Davies respecting Tables of Longitude, 1790 October 2

This folder contains two handwritten agreements concerning the exchange of mathematical calculations by Nathan Davies for copies of Croswell's published tables of longitude.

Economic Partnership Agreements in the EU's post-Lome trade regime: negotiations with West Africa. ZEI Discussion Paper C214, 2012

Trade is a key element of the development policy of the European Union (EU). As the most important trading partner of developing countries, the EU attempts to facilitate the participation of developing countries in global trade and contribute to economic growth through providing market access and financial assistance. For twenty-five years, the commitment of the EU was largely focused on its former colonies, more specifically in Africa, the Caribbean and the Pacific (ACP). The developing world, in terms of the EU’s trade policy, was therefore divided between ACP states with special provisions under the Lomé Conventions and all other developing countries. With the new millennium, this special relationship came to an end. Pressure from several member states1 and the World Trade Organization (WTO) led to an overhaul of the EU’s trade regime vis-à-vis developing countries and to the loss of the privileged position of ACP countries. The result of this overhaul is still pending. Economic Partnership Agreements (EPAs) – to be negotiated between the EU and several ACP regions – have only been realized in the Caribbean. This article will to examine the negotiations between the EU and West Africa and discuss the interests involved on the African side. Following the introduction, the second part of this article is dedicated to the Lomé Conventions with a focus on the change occurring from the third to the fourth revision in order to understand the current situation. The third part is going to take a look at the Cotonou agreement and the trade regime of the EU in general before turning to the negotiations for an Economic Partnership Agreement between the EU and West Africa. The conclusion summarizes the main findings.

Reform der EU-Wettbewerbsregeln für Technologietransfer-Verträge: Einfahrt in den sicheren Hafen? = Reform of EU competition rules on technology transfer agreements: entry into the safe harbor? Research Paper in Law 2/2004

No abstract.