Multiple programmed cell death pathways are involved in N-methyl-N-nitrosourea-induced photoreceptor degeneration.

PURPOSE: To identify programmed cell death (PCD) pathways involved in N-methyl-N-nitrosourea (MNU)-induced photoreceptor (PR) degeneration. METHODS: Adult C57BL/6 mice received a single MNU i.p. injection (60 mg/kg bodyweight), and were observed over a period of 7 days. Degeneration was visualized by H&E overview staining and electron microscopy. PR cell death was measured by quantifying TUNEL-positive cells in the outer nuclear layer (ONL). Activity measurements of key PCD enzymes (calpain, caspases) were used to identify the involved cell death pathways. Furthermore, the expression level of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78), key players in endoplasmic reticulum (ER) stress-induced apoptosis, was analyzed using quantitative real-time PCR. RESULTS: A decrease in ONL thickness and the appearance of apoptotic PR nuclei could be detected beginning 3 days post-injection (PI). This was accompanied by an increase of TUNEL-positive cells. Significant upregulation of activated caspases (3, 9, 12) was found at different time periods after MNU injection. Additionally, several other players of nonconventional PCD pathways were also upregulated. Consequently, calpain activity increased in the ONL, with a maximum on day 7 PI and an upregulation of CHOP and GRP78 expression beginning on day 1 PI was found. CONCLUSIONS: The data indicate that regular apoptosis is the major cause of MNU-induced PR cell death. However, alternative PCD pathways, including ER stress and calpain activation, are also involved. Knowledge about the mechanisms involved in this mouse model of PR degeneration could facilitate the design of putative combinatory therapeutic approaches.

Connecting and Educating Hindus: Hinduism Today and the Mediatization of a Global Hinduism

Hinduism Today is a quarterly magazine that appears in roughly 15.000 copies, shipped to nearly 60 countries worldwide. The majority of readers are Hindus in diverse diaspora countries, mainly Singapur, Malaysia, Mauritius, Trinidad und the USA. Its editors are monks of Kauai Adheenam, belonging to the Śaiva Siddhānta Church, situated in Kauai, Hawai’i, USA. One of the magazine’s declared goals is to foster global Hindu solidarity and educate Hindus worldwide about their religion. In this paper, I want to take a look at the history of this magazine in connection with the Śaiva Siddhānta Church, and at the development of the expressed aims behind its publication. For this, I draw on fieldwork done in Kauai in January, 2014. After a brief introduction to some theoretical and methodological preliminaries of my work, I shall, give an overview of the history of the Śaiva Siddhānta Church, founded by Satguru Sivaya Subramuniyaswami. Following this, I will deal in more detail with the origins and development of the magazine and the websites connected with it. I will focus especially on the role the magazine was intended to play for global Hindu diasporas. A fourth chapter will analyze the modes of definition employed in order to depict Hinduism as a unified global religion. In conclusion, I shall briefly reflect upon the specific agenda of “Global Hinduism” and the strategies of positioning as followed by the publishers of Hinduism Today.

From Connecting Hindus to Uniting Global Hinduism: History and Guiding Principles of Hinduism Today

Hinduism Today is a quarterly magazine that appears in roughly 15.000 copies, shipped to nearly 60 countries worldwide. The majority of readers are Hindus in diverse diaspora countries, mainly Singapur, Malaysia, Mauritius, Trinidad und the USA. Its editors are monks of Kauai Adheenam, belonging to the Śaiva Siddhānta Church, situated in Kauai, Hawai’i, USA. One of the magazine’s declared goals is to foster global Hindu solidarity and educate Hindus worldwide about their religion. In this paper, I want to take a look at the history of this magazine in connection with the Śaiva Siddhānta Church, and at the development of the expressed aims behind its publication. For this, I draw on fieldwork done in Kauai in January, 2014. After a brief introduction to some theoretical and methodological preliminaries of my work, I shall, give an overview of the history of the Śaiva Siddhānta Church, founded by Satguru Sivaya Subramuniyaswami. Following this, I will deal in more detail with the origins and development of the magazine and the websites connected with it. I will focus especially on the role the magazine was intended to play for global Hindu diasporas. A fourth chapter will analyze the modes of definition employed in order to depict Hinduism as a unified global religion. In conclusion, I shall briefly reflect upon the specific agenda of “Global Hinduism” and the strategies of positioning as followed by the publishers of Hinduism Today.

Characterization of the NOP -1 opsin photoreceptor in the filamentous fungus Neurospora crassa

Light absorption is an important process for energy production and sensory perception in many organisms. In the filamentous fungus, Neurospora crassa, blue-light is an important regulator of both asexual and sexual development, but the identity of the blue-light receptor is unknown. The work presented in this dissertation initiated the characterization of the putative N. crassa opsin photoreceptor, NOP-1. Opsins were thought to exist only in the archaea and mammals until the discovery of nop-1. All opsins have the same conserved structure of seven transmembrane helical domains with a lysine residue in the seventh helix specific for forming a Schiff-base linkage with retinal. The predicted NOP-1 protein sequence is equally similar to archaeal rhodopsins and a newly identified fungal opsin-related protein group (ORPs). ORPs maintain the seven transmembrane helical structure of opsins, but lack the conserved lysine residue for binding retinal. An ORP gene, orp-1 was identified in N. crassa and this work includes the cloning and sequence analysis of this gene. Characterization of NOP-1 function in N. crassa development began with the construction of a Δnop-1 deletion mutant. Extensive phenotypic analysis of Δnop-1 mutants revealed only subtle defects during development primarily under environmental conditions that induce a stress response. NOP-1 was overexpressed in the heterologous system Pichia pastoris, and it was demonstrated that NOP-1 protein bound all-trans retinal to form a green-light absorbing pigment (λmax = 534 nm) with a photochemical reaction cycle similar to archaeal sensory rhodopsins. nop-1 gene expression was monitored during N. crassa development. nop-1 transcript is highly expressed during asexual sporulation (conidiation) and transcript levels are abundant in the later stages of conidial development. nop-1 expression is not regulated by blue-light or elevated temperatures. Potential functions for NOP-1 were discovered through the transcriptional analysis of conidiation-associated genes in Δnop-1 mutants. NOP-1 exhibits antagonistic transcriptional regulation of conidiation-associated genes late in conidial development, by enhancing the carotenogenic gene, al-2 and repressing the conidiation-specific genes, con-10 and con-13. ^

The Darién Region, Connecting Road of the Americas, among the expressions of hydric wealth, land vocation and the extractive exploration on its violated forms

Colombia has oceanic waters, catchment areas, like lakes, cienagas and swamps, water flows, like rivers, gorges and streams, small rivers and groundwater. The oceanic waters are the Caribbean Sea-1600 km and the Pacific Ocean-1300 km that comprise the north and west continental territory, respectively. Actually the Region of Darién, geographically bounded by the Carribean Sea to the north is becoming to be focused by studies due to use conflicts and disputes about water and a forest reserve on its territories. Considering its location, strategic at northwestern Colombia, frontier region with Central America, several dynamics are imposed. One of them is the implantation of a road system entitled Connecting Road of the Americas. This fact means the construction of an infra-structure that will cross a special zone formed by swamps and jungle known as The Darién Gap. Evidences of such interests are revealed by projects like the constructions of Turbo's Port in the Atlantic Ocean, Department of Antioquia and Tribugá's Port in the Pacific Ocean, Department of Choco, the mountain road and the coastal conection Colombia-Venezuela attending to the main intentions of the central region of the department (Metropolitan Area of Aburrá Valley-AMVA). Human settlements form a productive system, based on small and medium familiar agriculture's production, corresponding to the western portion and piedmont of Abibe's mountain at its antioquian portion, alluvial plan that forms the rivers on this area, the littoral zone that delimits the Carribean Sea, the Darién and Baudó Mountains and the gulf that receives, among other waters, the ones from Atrato and León, as well as the exodus process constitutes a forced exit resulting from actions of several armed groups. It can be identified intense historical, cultural, political and environmental relations, specially the last one associated with strategic ecosystems that are fundamental for the hydric regulation of the region, as well as food safety of the local inhabitants. Results from two researches (UPB, 2007 y 2010) reveals this quick transformation in the spatial re-configuration, demographical and economical indicators and the exacerbated fight for resources, damaging the extractive vocation in the Region. Path to commerce of illegalities (drugs, guns) and to implementation of the agroindustrial project for biofuel production, cooperation program that involves Venezuela, Brazil and Colombia. Appropriation modes allow the existence of strategies since global interests revealing a development logic that privileges the conception of an artificialized nature. Since the smallest portion of rural areas, specific modes of resources exploration are linked to imposed interests of transnational corporations. Disparate consequences are going deeper evidenced by social, technical and nature transformations, envisioning risks for the habitability's condition

The Darién Region, Connecting Road of the Americas, among the expressions of hydric wealth, land vocation and the extractive exploration on its violated forms

Colombia has oceanic waters, catchment areas, like lakes, cienagas and swamps, water flows, like rivers, gorges and streams, small rivers and groundwater. The oceanic waters are the Caribbean Sea-1600 km and the Pacific Ocean-1300 km that comprise the north and west continental territory, respectively. Actually the Region of Darién, geographically bounded by the Carribean Sea to the north is becoming to be focused by studies due to use conflicts and disputes about water and a forest reserve on its territories. Considering its location, strategic at northwestern Colombia, frontier region with Central America, several dynamics are imposed. One of them is the implantation of a road system entitled Connecting Road of the Americas. This fact means the construction of an infra-structure that will cross a special zone formed by swamps and jungle known as The Darién Gap. Evidences of such interests are revealed by projects like the constructions of Turbo's Port in the Atlantic Ocean, Department of Antioquia and Tribugá's Port in the Pacific Ocean, Department of Choco, the mountain road and the coastal conection Colombia-Venezuela attending to the main intentions of the central region of the department (Metropolitan Area of Aburrá Valley-AMVA). Human settlements form a productive system, based on small and medium familiar agriculture's production, corresponding to the western portion and piedmont of Abibe's mountain at its antioquian portion, alluvial plan that forms the rivers on this area, the littoral zone that delimits the Carribean Sea, the Darién and Baudó Mountains and the gulf that receives, among other waters, the ones from Atrato and León, as well as the exodus process constitutes a forced exit resulting from actions of several armed groups. It can be identified intense historical, cultural, political and environmental relations, specially the last one associated with strategic ecosystems that are fundamental for the hydric regulation of the region, as well as food safety of the local inhabitants. Results from two researches (UPB, 2007 y 2010) reveals this quick transformation in the spatial re-configuration, demographical and economical indicators and the exacerbated fight for resources, damaging the extractive vocation in the Region. Path to commerce of illegalities (drugs, guns) and to implementation of the agroindustrial project for biofuel production, cooperation program that involves Venezuela, Brazil and Colombia. Appropriation modes allow the existence of strategies since global interests revealing a development logic that privileges the conception of an artificialized nature. Since the smallest portion of rural areas, specific modes of resources exploration are linked to imposed interests of transnational corporations. Disparate consequences are going deeper evidenced by social, technical and nature transformations, envisioning risks for the habitability's condition

The Darién Region, Connecting Road of the Americas, among the expressions of hydric wealth, land vocation and the extractive exploration on its violated forms

Colombia has oceanic waters, catchment areas, like lakes, cienagas and swamps, water flows, like rivers, gorges and streams, small rivers and groundwater. The oceanic waters are the Caribbean Sea-1600 km and the Pacific Ocean-1300 km that comprise the north and west continental territory, respectively. Actually the Region of Darién, geographically bounded by the Carribean Sea to the north is becoming to be focused by studies due to use conflicts and disputes about water and a forest reserve on its territories. Considering its location, strategic at northwestern Colombia, frontier region with Central America, several dynamics are imposed. One of them is the implantation of a road system entitled Connecting Road of the Americas. This fact means the construction of an infra-structure that will cross a special zone formed by swamps and jungle known as The Darién Gap. Evidences of such interests are revealed by projects like the constructions of Turbo's Port in the Atlantic Ocean, Department of Antioquia and Tribugá's Port in the Pacific Ocean, Department of Choco, the mountain road and the coastal conection Colombia-Venezuela attending to the main intentions of the central region of the department (Metropolitan Area of Aburrá Valley-AMVA). Human settlements form a productive system, based on small and medium familiar agriculture's production, corresponding to the western portion and piedmont of Abibe's mountain at its antioquian portion, alluvial plan that forms the rivers on this area, the littoral zone that delimits the Carribean Sea, the Darién and Baudó Mountains and the gulf that receives, among other waters, the ones from Atrato and León, as well as the exodus process constitutes a forced exit resulting from actions of several armed groups. It can be identified intense historical, cultural, political and environmental relations, specially the last one associated with strategic ecosystems that are fundamental for the hydric regulation of the region, as well as food safety of the local inhabitants. Results from two researches (UPB, 2007 y 2010) reveals this quick transformation in the spatial re-configuration, demographical and economical indicators and the exacerbated fight for resources, damaging the extractive vocation in the Region. Path to commerce of illegalities (drugs, guns) and to implementation of the agroindustrial project for biofuel production, cooperation program that involves Venezuela, Brazil and Colombia. Appropriation modes allow the existence of strategies since global interests revealing a development logic that privileges the conception of an artificialized nature. Since the smallest portion of rural areas, specific modes of resources exploration are linked to imposed interests of transnational corporations. Disparate consequences are going deeper evidenced by social, technical and nature transformations, envisioning risks for the habitability's condition

Idiopathic multifocal choroiditis/punctate inner choroidopathy with acute photoreceptor loss or dysfunction out of proportion to clinically visible lesions.

PURPOSE To report acute/subacute vision loss and paracentral scotomata in patients with idiopathic multifocal choroiditis/punctate inner choroidopathy due to large zones of acute photoreceptor attenuation surrounding the chorioretinal lesions. METHODS Multimodal imaging case series. RESULTS Six women and 2 men were included (mean age, 31.5 ± 5.8 years). Vision ranged from 20/20-1 to hand motion (mean, 20/364). Spectral domain optical coherence tomography demonstrated extensive attenuation of the external limiting membrane, ellipsoid and interdigitation zones, adjacent to the visible multifocal choroiditis/punctate inner choroidopathy lesions. The corresponding areas were hyperautofluorescent on fundus autofluorescence and were associated with corresponding visual field defects. Full-field electroretinogram (available in three cases) showed markedly decreased cone/rod response, and multifocal electroretinogram revealed reduced amplitudes and increased implicit times in two cases. Three patients received no treatment, the remaining were treated with oral corticosteroids (n = 4), oral acyclovir/valacyclovir (n = 2), intravitreal/posterior subtenon triamcinolone acetate (n = 3), and anti-vascular endothelial growth factor (n = 2). Visual recovery occurred in only three cases of whom two were treated. Varying morphological recovery was found in six cases, associated with decrease in hyperautofluorescence on fundus autofluorescence. CONCLUSION Multifocal choroiditis/punctate inner choroidopathy can present with transient or permanent central photoreceptor attenuation/loss. This presentation is likely a variant of multifocal choroiditis/punctate inner choroidopathy with chorioretinal atrophy. Associated changes are best evaluated using multimodal imaging.

Border Trade and Economic Zones on the North-South Economic Corridor: Focusing on the Connecting Points between the Four Countries

The North-South Economic Corridor (NSEC), the road between Bangkok and Kunming, China, including the Laos route (R3B) and the Myanmar route (R3B), has been developed since 1998 following the GMS program. The region covering Yunnan Province in China, Shan State in Myanmar, Northern Laos and Northern Thailand has historical and ethnic closeness, and is a comparatively poor mountainous, boundary area. In the wake of the development of the NSEC, however, the region has started to show signs of change. Consequently, a review is to be carried out concerning the movement of people and cars, border trade and the situation concerning the progress of border economic zones at the five nodal border points in the four countries, and over three routes: R3A, R3B, and the Mekong River route.

Connecting red cells in a bichromatic Voronoi diagram

Let S be a set of n + m sites, of which n are red and have weight wR, and m are blue and weigh wB. The objective of this paper is to calculate the minimum value of wR such that the union of the red Voronoi cells in the weighted Voronoi diagram of S is a connected set. The problem is solved for the multiplicatively-weighted Voronoi diagram in O((n+m)^2 log(nm)) time and for the additively-weighted Voronoi diagram in O(nmlog(nm)) time.

An isoform of the rod photoreceptor cyclic nucleotide-gated channel β subunit expressed in olfactory neurons

Sensory transduction in olfactory neurons involves the activation of a cyclic nucleotide-gated (CNG) channel by cAMP. Previous studies identified a CNG channel α subunit (CNG2) and a β subunit (CNG5), which when heterologously expressed form a channel with properties similar but not identical to those of native olfactory neurons. We have cloned a new type of CNG channel β subunit (CNG4.3) from rat olfactory epithelium. CNG4.3 derives from the same gene as the rod photoreceptor β subunit (CNG4.1) but lacks the long, glutamic acid-rich domain found in the N terminus of CNG4.1. Northern blot and in situ hybridization revealed that CNG4.3 is expressed specifically in olfactory neurons. Expression of CNG4.3 in human embryonic kidney 293 cells did not lead to detectable currents. Coexpression of CNG4.3 with CNG2 induced a current with significantly increased sensitivity for cAMP whereas cGMP affinity was not altered. Additionally, CNG4.3 weakened the outward rectification of the current in the presence of extracellular Ca2+, decreased the relative permeability for Ca2+, and enhanced the sensitivity for l-cis diltiazem. Upon coexpression of CNG2, CNG4.3, and CNG5, a conductance with a cAMP sensitivity greater than that of either the CNG2/CNG4.3 or the CNG2/CNG5 channel and near that of native olfactory channel was observed. Our data suggest that CNG4.3 forms a subunit of the native olfactory CNG channel. The expression of various CNG4 isoforms in retina and olfactory epithelium indicates that the CNG4 subunit may be necessary for normal function of both photoreceptor and olfactory CNG channels.

trans/cis (Z/E) photoisomerization of the chromophore of photoactive yellow protein is not a prerequisite for the initiation of the photocycle of this photoreceptor protein

The chromophore of photoactive yellow protein (PYP) (i.e., 4-hydroxycinnamic acid) has been replaced by an analogue with a triple bond, rather than a double bond (by using 4-hydroxyphenylpropiolic acid in the reconstitution, yielding hybrid I) and by a “locked” chromophore (through reconstitution with 7-hydroxycoumarin-3-carboxylic acid, in which a covalent bridge is present across the vinyl bond, resulting in hybrid II). These hybrids absorb maximally at 464 and 443 nm, respectively, which indicates that in both hybrids the deprotonated chromophore does fit into the chromophore-binding pocket. Because the triple bond cannot undergo cis/trans (or E/Z) photoisomerization and because of the presence of the lock across the vinyl double bond in hybrid II, it was predicted that these two hybrids would not be able to photocycle. Surprisingly, both are able. We have demonstrated this ability by making use of transient absorption, low-temperature absorption, and Fourier-transform infrared (FTIR) spectroscopy. Both hybrids, upon photoexcitation, display authentic photocycle signals in terms of a red-shifted intermediate; hybrid I, in addition, goes through a blue-shifted-like intermediate state, with very slow kinetics. We interpret these results as further evidence that rotation of the carbonyl group of the thioester-linked chromophore of PYP, proposed in a previous FTIR study and visualized in recent time-resolved x-ray diffraction experiments, is of critical importance for photoactivation of PYP.