Assembly and disassembly of the Golgi Complex: two prodesses arranged in a cis to trans direction

We have studied the disassembly and assembly of two morphologically and functionally distinct parts of the Golgi complex, the cis/middle and trans cisterna/trans network compartments. For this purpose we have followed the redistribution of three cis/middle- (GMPc-1, GMPc-2, MG 160) and two trans- (GMPt-1 and GMPt-2) Golgi membrane proteins during and after treatment of normal rat kidney (NRK) cells with brefeldin A (BFA). BFA induced complete disassembly of the cis/middle- and trans-Golgi complex and translocation of GMPc and GMPt to the ER. Cells treated for short times (3 min) with BFA showed extensive disorganization of both cis/middle- and trans-Golgi complexes. However, complete disorganization of the trans part required much longer incubations with the drug. Upon removal of BFA the Golgi complex was reassembled by a process consisting of three steps: (a) exist of cis/middle proteins from the ER and their accumulation into vesicular structures scattered throughout the cytoplasm; (b) gradual relocation and accumulation of the trans proteins in the vesicles containing the cis/middle proteins; and (c) assembly of the cisternae, and reconstruction of the Golgi complex within an area located in the vicinity of the centrosome from which the ER was excluded. Reconstruction of the cis/middle-Golgi complex occurred under temperature conditions inhibitory of the reorganization of the trans-Golgi complex, and was dependent on microtubules. Reconstruction of the trans-Golgi complex, disrupted with nocodazole after selective fusion of the cis/middle-Golgi complex with the ER, occurred after the release of cis/middle-Golgi proteins from the ER and the assembly of the cis/middle cisternae.

Gp74 a membrane glycoprotein of the cis-Golgi network that cycles through the endoplasmic reticulum and intermediate compartment

A monoclonal antibody CC92 (IgM), raised against a fraction of rat liver enriched in Golgi membranes, recognizes a novel Endo H-resistant 74-kD membrane glycoprotein (gp74). The bulk of gp74 is confined to the cis-Golgi network (CGN). Outside the Golgi gp74 is found in tubulovesicular structures and ER foci. In cells incubated at 37 degrees C the majority of gp74 is segregated from the intermediate compartment (IC) marker p58. However, in cells treated with organelle perturbants such as low temperature, BFA, and [AIF4]- the patterns of the two proteins become indistinguishable. Both proteins are retained in the Golgi complex at 20 degrees C and in the IC at 15 degrees C. Incubation of cells with BFA results in relocation of gp74 to p58 positive IC elements. [AIF4]- induces the redistribution of gp74 from the Golgi to p58-positive vesicles and does not retard the translocation of gp74 to IC elements in cells treated with BFA. Disruption of microtubules by nocodazol results in the rapid disappearance of the Golgi elements stained by gp74 and redistribution of the protein into vesicle-like structures. The responses of gp74 to cell perturbants are in sharp contrast with those of cis/middle and trans-Golgi resident proteins whose location is not affected by low temperatures or [AIF4]-, are translocated to the ER upon addition of BFA, and stay in slow disintegrating Golgi elements in cells treated with nocodazol. The results suggest that gp74 is an itinerant protein that resides most of the time in the CGN and cycles through the ER/IC following the pathway used by p58.

Late Neogene lacustrine record and paleogeography in the Quillagua-Llamara basin, Central Andean fore-arc (Northern Chile)

The Cenozoic QuillaguaLlamara basin (northern Chile, Central Andes) is an asymmetrical, intramassif fore-arc basin with a relatively wide northern sector separated from a narrower southward extension by a basement threshold. The north- ern sector was characterised by a noticeable Oligocene?late Neogene alluvial-fan and lacustrine dominated deposition which resulted in sequences up to 900 m thick, whereas the southern sector was often a bypass zone with thinner fluvial and lacustrine sediment accumulation.

Natalizumab versus Interferon B-1b to prevent CDMS in patients with CIS and poor prognostic factors: research protocol

About 85% of multiple sclerosis (MS) cases start as clinically isolated syndrome (CIS).When patients present with a CIS, clinicians face with many questions, most of themrelated with prognosis and treatment. Thereby, patients with CIS have been focus ofresearch. Several studies have demonstrated a relationship between positive IgM lipidspecific oligoclonal band pattern in CSF and higher lesion load on MRI brain scan, higher number of relapses and greater disability, even at the first stages of the disease. On the other hand, no studies have used this previous evidence to treat with more aggressive disease modifying therapy in initial stages of disease course to prevent the earlier axonal damage. The aim of this study is to assess the most effective approved treatment for MS and current therapy for CIS patients presenting high risk to develop CDMS and with biomarkers of poor prognosis. Among this group of patients any disease activity will eventually lead to disability. Therefore, the earlier the treatment is initiated, the more effective to prevent disability will be. It is considered that “time lost is brain lost” and since once damage is established, there is no therapy to be regained later on. In this phase III clinical trial, 172 patients will be randomized 1:1 to receive Interferon β-1b or natalizumab over 96 weeks. Time to develop clinical definitive multiple sclerosis (CDMS) will be included as primary endpoint. Other secondary endpoints will include clinical data, magnetic resonance imaging (MRI) measurements and quality of life tests

Natalizumab versus Interferon B-1b to prevent CDMS in patients with CIS and poor prognostic factors: research protocol

About 85% of multiple sclerosis (MS) cases start as clinically isolated syndrome (CIS).When patients present with a CIS, clinicians face with many questions, most of themrelated with prognosis and treatment. Thereby, patients with CIS have been focus ofresearch. Several studies have demonstrated a relationship between positive IgM lipidspecific oligoclonal band pattern in CSF and higher lesion load on MRI brain scan, higher number of relapses and greater disability, even at the first stages of the disease. On the other hand, no studies have used this previous evidence to treat with more aggressive disease modifying therapy in initial stages of disease course to prevent the earlier axonal damage. The aim of this study is to assess the most effective approved treatment for MS and current therapy for CIS patients presenting high risk to develop CDMS and with biomarkers of poor prognosis. Among this group of patients any disease activity will eventually lead to disability. Therefore, the earlier the treatment is initiated, the more effective to prevent disability will be. It is considered that “time lost is brain lost” and since once damage is established, there is no therapy to be regained later on. In this phase III clinical trial, 172 patients will be randomized 1:1 to receive Interferon β-1b or natalizumab over 96 weeks. Time to develop clinical definitive multiple sclerosis (CDMS) will be included as primary endpoint. Other secondary endpoints will include clinical data, magnetic resonance imaging (MRI) measurements and quality of life tests

Lake-level and salinity reconstruction from diatom analyses in Quillagua Formation (Late Neogene, Central Andean Forearc, Northern Chile)

A sedimentary and micropaleontological study of the Quillagua Formation provides a detailed paleohydrological reconstruction of the lacustrine system which occupied the present-day hyperarid Quillagua-Llamara fore-arc Basin (Northern Chile) from lattermost Miocene to Early Pliocene times.

An enantioselective synthetic route to cis-2,4-disubstituted and 2,4-bridged piperidines

A synthetic route to enantiopure cis-2,4-disubstituted and 2,4-bridged piperidines is reported, the key step being a stereoselective conjugate addition of an organocuprate to a phenylglycinol-derived unsaturated lactam bearing a substituent at the 8a-position.

Distribution, Abundance and Molecular Analysis of Genus Barbadocladius Cranston & Krosch (Diptera, Chironomidae) in Tropical, High Altitude Andean Streams and Rivers

The distribution of the genus Barbadocladius Cranston & Krosch (Diptera: Chironomidae), previously reported from Chile to Bolivia, has extended northwards. Larvae, pupae and pupal exuviae of this genus have been found in the high mountain tropical streams of Peru to 9°22′56″, but are restricted to very high altitude streams (altitudes over 3,278 m asl) compared to the lower altitude streams (below 1,100 m asl) in which the genus is reported in Chile and Argentina. Based on morphological studies, both described species in the genus, Barbadocladius andinus Cranston & Krosch and Barbadocladius limay Cranston & Krosch, have been found in Peru as pupae or pupal exuviae. Morphological analysis of the larvae and pupae revealed no differences between the two described species from Patagonia and Peru, which are of similar size and with a similar armament of hooklets and spines in pupal tergites and sternites. However, molecular analysis of larvae and pupae revealed that in Peru, there are at least two different evolutionary lines, one distributed widely and another restricted to one site. Phylogenetic analysis (using cox1 mitochondrial sequences) of all available sequences of Barbadocladius shows that the Chilean and Argentinean material differs from that of Peru. Therefore, a total of four molecular segregates are identified, although morphologically, neither larvae nor the pupae may be differentiated.

An enantioselective entry to cis-perhydroisoquinolines

An enantioselective route to cis-perhydroisoquinolines, involving a cyclocondensation reaction of (R)-phenylglycinol with a racemic oxoester, a stereoselective conjugate addition to an unsaturated bicyclic lactam, and the closure of the carbocyclic ring by a ring-closing metathesis as the key steps is reported. This route allows the preparation of 3-cyano derivatives as well as cis-octahydroisoquinolines bearing a quaternary center at the C4-position.

Competition in notch signaling with cis enriches cell fate decisions

Notch signaling is involved in cell fate choices during the embryonic development of Metazoa. Commonly, Notch signaling arises from the binding of the Notch receptor to its ligands in adjacent cells driving cell-to-cell communication. Yet, cell-autonomous control of Notch signaling through both ligand-dependent and ligand-independent mechanisms is known to occur as well. Examples include Notch signaling arising in the absence of ligand binding, and cis-inhibition of Notch signaling by titration of the Notch receptor upon binding to its ligands within a single cell. Increasing experimental evidences support that the binding of the Notch receptor with its ligands within a cell (cis-interactions) can also trigger a cell-autonomous Notch signal (cis-signaling), whose potential effects on cell fate decisions and patterning remain poorly understood. To address this question, herein we mathematically and computationally investigate the cell states arising from the combination of cis-signaling with additional Notch signaling sources, which are either cell-autonomous or involve cell-to-cell communication. Our study shows that cis-signaling can switch from driving cis-activation to effectively perform cis-inhibition and identifies under which conditions this switch occurs. This switch relies on the competition between Notch signaling sources, which share the same receptor but differ in their signaling efficiency. We propose that the role of cis-interactions and their signaling on fine-grained patterning and cell fate decisions is dependent on whether they drive cis-inhibition or cis-activation, which could be controlled during development. Specifically, cis-inhibition and not cis-activation facilitates patterning and enriches it by modulating the ratio of cells in the high-ligand expression state, by enabling additional periodic patterns like stripes and by allowing localized patterning highly sensitive to the precursor state and cell-autonomous bistability. Our study exemplifies the complexity of regulations when multiple signalng sources share the same receptor and provides the tools for their characterization.

The Andean Biotic Index (ABI): revised tolerance to pollution values for macroinvertebrate families and index performance evaluation.

Score-based biotic indices are widely used to evaluate the water quality of streams and rivers. Few adaptations of these indices have been done for South America because there is a lack of knowledge on mac-roinvertebrate taxonomy, distribution and tolerance to pollution in the region. Several areas in the Andes are densely populated and there is need for methods to assess the impact of increasing human pressures on aquatic ecosystems. Considering the unique ecological and geographical features of the Andes, macroinvertebrate indices used in other regions must be adapted with caution. Here we present a review of the literature on mac-roinvertebrate distribution and tolerance to pollution in Andean areas above 2 000masl. Using these data, we propose an Andean Biotic Index (ABI), which is based on the BMWP index. In general, ABI includes fewer macroinvertebrate families than in other regions of the world where the BMWP index has been applied because altitude restricts the distribution of several families. Our review shows that in the high Andes, the tolerance of several macroinvertebrate families to pollution differs from those reported in other areas. We tested the ABI index in two basins in Ecuador and Peru, and compared it to other BMWP adaptations using the reference condi-tion approach. The ABI index is extremely useful for detecting the general impairment of rivers but class quality boundaries should be defined independently for each basin because reference conditions may be different. The ABI is widely used in Ecuador and Peru, with high correlations with land-use pressures in several studies. The ABI index is an integral part of the new multimetric index designed for high Andean streams (IMEERA). Rev. Biol. Trop. 62 (Suppl. 2): 249-273. Epub 2014 April 01.

The Experience of European Integration and the Potential for Integration in South America

The experience of the European Union is the most significant and far-reaching among all attempts at regional integration. It is, therefore, the most likely to provide some lessons for those world regions that are just beginning this complex process. In turn, the Common Market of the South (MERCOSUR) and the Andean Community (CAN) are among the regional integration projects that have reached the greatest level of formal accomplishment after the EU. MERCOSUR is a customs union that aspires to become a common market, while avowing the commitment to advance towards political integration. For its part, CAN is a customs union that has already developed supranational institutions such as a Commission, a Parliament and a Court of Justice. In both cases, however, words have progressively tended to wander far from deeds. One reason underlying this phenomenon may be a misunderstanding of the European experience with integration. In this article, we discuss the theories that have been developed to account for integration in Europe and may prove useful to understand integration elsewhere and put forward a set of lessons that could be drawn from the European experience. Subsequently, we introduce a description of the experience of integration in South America and reflect (critically) on how the theories and lessons drawn from the EU could be applied to this region –and beyond.

Barriers to innovation and public policy in Catalonia

The present paper analyses the link between firms’ decisions to innovate and the barriers that prevent them from being innovative. The aim is twofold. First, it analyses three groups of barriers to innovation: the cost of innovation projects, lack of knowledge and market conditions. Second, it presents the main steps taken by Catalan Government to promote the creation of new firms and to reduce barriers to innovation. The data set used is based on the 2004 official innovation survey of Catalonia which was taken from the Spanish CIS-4 sample. This sample includes individual information on 2,954 Catalan firms in manufacturing industries and knowledge-intensive services (KIS). The empirical analysis reveals pronounced differences regarding a firm’s propensity to innovate and its perception of barriers. Moreover, the results show that cost and knowledge barriers seem to be the most important and that there are substantial sectoral differences in the way that firms react to barriers. The results of this paper have important implications for the design of future public policy to promote entrepreneurship and innovation together.

Valoración del estudio vesical y del tracto urinario superior en pacientes con citología urinaria positiva y pruebas de imagen negativas

Introducció: La citologia urinària positiva en context de cistoscopia sense evidència de tumor macroscòpic obliga a continuar el seu estudi. En el nostre centre es realitzen biòpsies vesicals múltiples normatitzades (BMN) i citologia ureteral selectiva en aquest casos. Material i mètodes: Estudi retrospectiu de 70 pacients amb citologia urinària positiva en absència de tumor macroscòpic. Es van avaluar els resultats de totes les biòpsies vesicals múltiples i les citologies ureterals selectives realitzades. Resultats: Es va diagnosticar CIS vesical em 45 (64,3%) pacients. Es va detectar citologia ureteral positiva em 12: cinc (7,2%) en el costat esquerre i set (10%) en el dret. Es va observar CIS vesical concomitant em 2 de 5 pacients amb PAP ureteral positiu esquerra i em 5 de 7 amb PAP ureteral positiu dret. Conclusions: La biòpsia múltiple normatitzada (BMN) és útil per a aquest casos. Els pobres resultats obtinguts en citologia ureteral selectiva posen en dubte la rendibilitat de la seva utilització sistemàtica.

High Growth Firms and Innovation: an empirical analysis for Spanish firms

This paper analyzes the effect of firms’ innovation activities on their growth performance. In particular, we observe how important innovation is for high-growth firms (HGFs) for an extensive sample of Spanish manufacturing and services firms. The panel data used comprises diverse waves of Spanish CIS over the the period 2004-2008. First, a probit analysis determines whether innovation affects the probability of being a high-growth firm. And second, a quantile regression technique is applied to explore the determinants and characteristics of specific groups of firms (manufacturing versus service firms and high-tech versus low-tech firms). It is revealed that R&D plays a significant role in the probability of becoming a HGF. Investment in internal and external R&D per employee has a positive impact on firm growth (although internal R&D presents a significant impact in the last quantiles, external R&D is significant up to the median). Furthermore, we show evidence that there is a positive impact of employment (sales) growth on the sales (employment) growth. Keywords: high-growth firms, firm growth, innovation activity JEL Classifications: L11, L25, O30