Continuous and lurching traveling pulses in neuronal networks with delay and spatially decaying connectivity

Propagation of discharges in cortical and thalamic systems, which is used as a probe for examining network circuitry, is studied by constructing a one-dimensional model of integrate-and-fire neurons that are coupled by excitatory synapses with delay. Each neuron fires only one spike. The velocity and stability of propagating continuous pulses are calculated analytically. Above a certain critical value of the constant delay, these pulses lose stability. Instead, lurching pulses propagate with discontinuous and periodic spatio-temporal characteristics. The parameter regime for which lurching occurs is strongly affected by the footprint (connectivity) shape; bistability may occur with a square footprint shape but not with an exponential footprint shape. For strong synaptic coupling, the velocity of both continuous and lurching pulses increases logarithmically with the synaptic coupling strength gsyn for an exponential footprint shape, and it is bounded for a step footprint shape. We conclude that the differences in velocity and shape between the front of thalamic spindle waves in vitro and cortical paroxysmal discharges stem from their different effective delay; in thalamic networks, large effective delay between inhibitory neurons arises from their effective interaction via the excitatory cells which display postinhibitory rebound.

Architecture of the Nuclear Periphery of Rat Pachytene Spermatocytes: Distribution of Nuclear Envelope Proteins in Relation to Synaptonemal Complex Attachment Sites

The nucleus of spermatocytes provides during the first meiotic prophase an interesting model for investigating relationships of the nuclear envelope (NE) with components of the nuclear interior. During the pachytene stage, meiotic chromosomes are synapsed via synaptonemal complexes (SCs) and attached through both ends to the nuclear periphery. This association is dynamic because chromosomes move during the process of synapsis and desynapsis that takes place during meiotic prophase. The NE of spermatocytes possesses some peculiarities (e.g., lower stability than in somatic cells, expression of short meiosis-specific lamin isoforms called C2 and B3) that could be critically involved in this process. For better understanding of the association of chromosomes with the nuclear periphery, in the present study we have investigated the distribution of NE proteins in relation to SC attachment sites. A major outcome was the finding that lamin C2 is distributed in the form of discontinuous domains at the NE of spermatocytes and that SC attachment sites are embedded in these domains. Lamin C2 appears to form part of larger structures as suggested by cell fractionation experiments. According to these results, we propose that the C2-containing domains represent local reinforcements of the NE that are involved in the proper attachment of SCs.

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.

A zinc finger-containing papain-like protease couples subgenomic mRNA synthesis to genome translation in a positive-stranded RNA virus

The genome expression of positive-stranded RNA viruses starts with translation rather than transcription. For some viruses, the genome is the only viral mRNA and expression is regulated primarily at the translational level and by limited proteolysis of polyproteins. Other virus groups also generate subgenomic mRNAs later in the reproductive cycle. For nidoviruses, subgenomic mRNA synthesis (transcription) is discontinuous and yields a 5′ and 3′ coterminal nested set of mRNAs. Nidovirus transcription is not essential for genome replication, which relies on the autoprocessing products of two replicase polyproteins that are translated from the genome. We now show that the N-terminal replicase subunit, nonstructural protein 1 (nsp1), of the nidovirus equine arteritis virus is in fact dispensable for replication but crucial for transcription, thereby coupling replicase expression and subgenomic mRNA synthesis in an unprecedented manner. Nsp1 is composed of two papain-like protease domains and a predicted N-terminal zinc finger, which was implicated in transcription by site-directed mutagenesis. The structural integrity of nsp1 is essential, suggesting that the protease domains form a platform for the zinc finger to operate in transcription.

SfiI endonuclease activity is strongly influenced by the non-specific sequence in the middle of its recognition site

The SfiI endonuclease cleaves DNA at the sequence GGCCNNNN↓NGGCC, where N is any base and ↓ is the point of cleavage. Proteins that recognise discontinuous sequences in DNA can be affected by the unspecified sequence between the specified base pairs of the target site. To examine whether this applies to SfiI, a series of DNA duplexes were made with identical sequences apart from discrete variations in the 5 bp spacer. The rates at which SfiI cleaved each duplex were measured under steady-state conditions: the steady-state rates were determined by the DNA cleavage step in the reaction pathway. SfiI cleaved some of these substrates at faster rates than other substrates. For example, the change in spacer sequence from AACAA to AAACA caused a 70-fold increase in reaction rate. In general, the extrapolated values for kcat and Km were both higher on substrates with inflexible spacers than those with flexible structures. The dinucleotide at the site of cleavage was largely immaterial. SfiI activity is thus highly dependent on conformational variations in the spacer DNA.

Does the granular matter?

Granular materials, such as sand, gravel, powders, and pharmaceutical pills, are large aggregates of macroscopic, individually solid particles, or “grains.” Far from being simple materials with simple properties, they display an astounding range of complex behavior that defies their categorization as solid, liquid, or gas. Just consider how sand can stream through the orifice of an hourglass yet support one's weight on the beach; how it can form patterns strikingly similar to a liquid when vibrated, yet respond to stirring by “unmixing” of large and small grains. Despite much effort, there still is no comprehensive understanding of other forms of matter, like ordinary fluids or solids. In what way, therefore, is granular matter special, and what makes it so difficult to understand? An emerging interdisciplinary approach to answering these questions focuses directly on the material's discontinuous granular nature.

The physiological significance of β-actin mRNA localization in determining cell polarity and directional motility

β-actin mRNA is localized near the leading edge in several cell types, where actin polymerization is actively promoting forward protrusion. The localization of the β-actin mRNA near the leading edge is facilitated by a short sequence in the 3′ untranslated region, the “zip code.” Localization of the mRNA at this region is important physiologically. Treatment of chicken embryo fibroblasts with antisense oligonucleotides complementary to the localization sequence (zip code) in the 3′ untranslated region leads to delocalization of β-actin mRNA, alteration of cell phenotype, and a decrease in cell motility. To determine the components of this process responsible for the change in cell behavior after β-actin mRNA delocalization, the Dynamic Image Analysis System was used to quantify movement of cells in the presence of sense and antisense oligonucleotides to the zip code. It was found that net path length and average speed of antisense-treated cells were significantly lower than in sense-treated cells. Total path length and the velocity of protrusion of antisense-treated cells were not affected compared with those of control cells. These results suggest that a decrease in persistence of direction of movement and not in velocity results from treatment of cells with zip code-directed antisense oligonucleotides. To test this, direct analysis of directionality was performed on antisense-treated cells and showed a decrease in directionality (net path/total path) and persistence of movement. Less directional movement of antisense-treated cells correlated with a unpolarized and discontinuous distribution of free barbed ends of actin filaments and of β-actin protein. These results indicate that delocalization of β-actin mRNA results in delocalization of nucleation sites and β-actin protein from the leading edge followed by loss of cell polarity and directional movement.

Increased accommodation of nascent RNA in a product site on RNA polymerase II during arrest.

RNA polymerases encounter specific DNA sites at which RNA chain elongation takes place in the absence of enzyme translocation in a process called discontinuous elongation. For RNA polymerase II, at least some of these sequences also provoke transcriptional arrest where renewed RNA polymerization requires elongation factor SII. Recent elongation models suggest the occupancy of a site within RNA polymerase that accommodates nascent RNA during discontinuous elongation. Here we have probed the extent of nascent RNA extruded from RNA polymerase II as it approaches, encounters, and departs an arrest site. Just upstream of an arrest site, 17-19 nucleotides of the RNA 3'-end are protected from exhaustive digestion by exogenous ribonuclease probes. As RNA is elongated to the arrest site, the enzyme does not translocate and the protected RNA becomes correspondingly larger, up to 27 nucleotides in length. After the enzyme passes the arrest site, the protected RNA is again the 18-nucleotide species typical of an elongation-competent complex. These findings identify an extended RNA product groove in arrested RNA polymerase II that is probably identical to that emptied during SII-activated RNA cleavage, a process required for the resumption of elongation. Unlike Escherichia coli RNA polymerase at a terminator, arrested RNA polymerase II does not release its RNA but can reestablish the normal elongation mode downstream of an arrest site. Discontinuous elongation probably represents a structural change that precedes, but may not be sufficient for, arrest by RNA polymerase II.

A Schistosoma mansoni fatty acid-binding protein, Sm14, is the potential basis of a dual-purpose anti-helminth vaccine.

Molecular cloning of components of protective antigenic preparations has suggested that related parasite fatty acid-binding proteins could form the basis of the protective immune crossreactivity between the parasitic trematode worms Fasciola hepatica and Schistosoma mansoni. Molecular models of the two parasite proteins showed that both molecules adopt the same basic three-dimensional structure, consisting of a barrel-shaped molecule formed by 10 antiparallel beta-pleated strands joined by short loops, and revealed the likely presence of crossreactive, discontinuous epitopes principally derived from amino acids in the C-terminal portions of the molecules. A recombinant form of the S. mansoni antigen, rSm14, protected outbred Swiss mice by up to 67% against challenge with S. mansoni cercariae in the absence of adjuvant and without provoking any observable autoimmune response. The same antigen also provided complete protection against challenge with F. hepatica metacercariae in the same animal model. The results suggest that it may be possible to produce a single vaccine that would be effective against at least two parasites, F. hepatica and S. mansoni, of veterinary and human importance, respectively.

Análise da estrutura populacional e do desequilíbrio de ligação de um painel de acessos de sorgo: uma abordagem usando teoria da coalescência

A estrutura populacional e o desequilíbrio de ligação são dois processos fundamentais para estudos evolutivos e de mapeamento associativo. Tradicionalmente, ambos têm sido investigados por meio de métodos clássicos comumente utilizados. Tais métodos certamente forneceram grandes avanços no entendimento dos processos evolutivos das espécies. No entanto, em geral, nenhum deles utiliza uma visão genealógica de forma a considerar eventos genéticos ocorridos no passado, dificultando a compreensão dos padrões de variação observados no presente. Uma abordagem que possibilita a investigação retrospectiva com base no atual polimorfismo observado é a teoria da coalescência. Assim, o objetivo deste trabalho foi analisar, com base na teoria da coalescência, a estrutura populacional e o desequilíbrio de ligação de um painel mundial de acessos de sorgo (Sorghum bicolor). Para tanto, análises de mutação, migração com fluxo gênico e recombinação foram realizadas para cinco regiões genômicas relacionadas à altura de plantas e maturidade (Dw1, Dw2, Dw4, Ma1 e Ma3) e sete populações previamente selecionadas. Em geral, elevado fluxo gênico médio (Μ = m/μ = 41,78 − 52,07) foi observado entre as populações considerando cada região genômica e todas elas simultaneamente. Os padrões sugeriram intenso intercâmbio de acessos e história evolutiva específica para cada região genômica, mostrando a importância da análise individual dos locos. A quantidade média de migrantes por geração (Μ) não foi simétrica entre pares recíprocos de populações, de acordo com a análise individual e simultânea das regiões. Isso sugere que a forma pela qual as populações se relacionaram e continuam interagindo evolutivamente não é igual, mostrando que os métodos clássicos utilizados para investigar estrutura populacional podem ser insatisfatórios. Baixas taxas médias de recombinação (ρL = 2Ner = 0,030 − 0,246) foram observadas utilizando o modelo de recombinação constante ao longo da região. Baixas e altas taxas médias de recombinação (ρr = 2Ner = 0,060 − 3,395) foram estimadas utilizando o modelo de recombinação variável ao longo da região. Os métodos tradicional (r2) e via coalescência (E[r2 rhomap]) utilizados para a estimação do desequilíbrio de ligação mostraram resultados próximos para algumas regiões genômicas e populações. No entanto, o r2 sugeriu padrões descontínuos de desequilíbrio em várias ocasiões, dificultando o entendimento e a caracterização de possíveis blocos de associação. O método via coalescência (E[r2 rhomap]) forneceu resultados que pareceram ter sido mais consistentes, podendo ser uma estratégia eventualmente importante para um refinamento dos padrões não-aleatórios de associação. Os resultados aqui encontrados sugerem que o mapeamento genético a partir de um único pool gênico pode ser insuficiente para detectar associações causais importantes para características quantitativas em sorgo.

Inovação e indústria da moda: um modelo de inovação em estilos e tendências.

Este trabalho tem como intuito propor um modelo de inovação para a indústria da moda feminina. O modelo visa compreender o comportamento de estilos e tendências determinados e difundidos pelas empresas. A construção deste modelo é justificada pela contribuição que um estudo sobre inovação pode proporcionar à indústria da moda, a qual enfrenta baixos padrões de competitividade no mercado externo e interno. Além disso, embora existam muitos artigos sobre o assunto, poucos foram os modelos de inovação para a indústria da moda encontrados por esta pesquisa. Uma avaliação destes modelos indicou que existe espaço para a proposta de um modelo que aborde o comportamento de estilos e tendências ao longo do tempo. A estrutura de composição do modelo é sustentada por três pilares conceituais: teoria econômica neoschumpeteriana, modelos de inovação e modelos de inovação para a indústria da moda. A característica central do modelo é avaliar se existem estilos que permanecem em moda de maneira contínua ou descontínua. Como existe similaridade conceitual entre os estilos, no que se refere à identidade de gênero (androginia e feminilidade), foi efetuada uma aglutinação de alguns estilos dentro desta denominação. Nem todos os estilos se encaixaram nesta classificação. Então, estes estilos foram denominados como neutros. Como a pesquisa tem abordagem fenomenológica, qualitativa e longitudinal, foi adotada a metodologia hipotética dedutiva para a construção do modelo. Para verificação da validade das hipóteses foi usada uma análise exploratória dos dados por meio de estatística descritiva e decomposição da estrutura de variabilidade através de uma análise de componentes principais (PCA). Ambas as análises forneceram evidências a respeito das hipóteses em questão, as quais também foram testadas através de um teste binomial e de uma análise de variância multivariada por meio de permutações. Os resultados comprovaram que existem estilos que permanecem em moda de maneira contínua e que existem períodos de polarização das aglutinações de estilo.

Resistência à abrasão de aço Hadfield para britadores: efeito do tamanho do abrasivo e do pH do meio.

Neste trabalho, foi investigado o efeito do tamanho do abrasivo e do pH do meio na resistência ao desgaste abrasivo do aço H-13 com matriz martensítica e do aço Hadfield com matriz austenítica. Ensaios de abrasão foram realizados utilizando o equipamento roda de borracha a úmido, variando o tamanho do abrasivo entre 0,15 e 2,40 mm e o pH do meio entre 5,5 e 12,8. As microestruturas dos materiais estudados foram analisadas utilizando microscopia óptica, as superfícies de desgaste e as partículas de desgaste foram analisadas em microscópio eletrônico de varredura. A macrodureza e a microdureza, antes e após os ensaios, foram obtidas utilizando durômetro Vickers. A topografia da região central da superfície de desgaste foi obtida utilizando Perfilometria 3D, visando obter valores de profundidade de penetração do abrasivo. Os resultados mostraram que o aço Hadfield é mais resistente do que o aço H-13 em todos os valores de pH e tamanhos de abrasivo utilizados. Para os dois materiais, a perda de massa aumenta linearmente até um tamanho crítico de abrasivo (TCA) e, após este, a mesma continua a aumentar, mas com uma intensidade menor. Para os dois materiais e para todos os tamanhos de abrasivo, o aumento do pH do meio resultou em menores perdas de massa, sendo este efeito maior para os dois menores tamanhos de abrasivo. Para maiores valores de pH, foram observadas menores profundidades de penetração do abrasivo. A microdureza da superfície de desgaste do aço H-13 sofreu um pequeno aumento com o aumento do tamanho do abrasivo enquanto que para o aço Hadfield esse aumento foi mais intenso. A análise das partículas de desgaste mostraram que, para todas as condições ensaiadas, os debris do aço H-13 tinham duas morfologias, contínuas e descontínuas enquanto que os cavacos do aço Hadfield foram sempre descontínuos. Para os dois materiais, foram observados dois micromecanismos de desgaste, sendo eles microcorte e microsulcamento. Por fim, os resultados apresentados neste trabalho sugerem que a análise de desempenho do aço Hadfield em serviço deve considerar o pH do meio bem como a granulometria do abrasivo em contato.

Evolución tectónica del borde norte de la cuenca del Bajo Segura. Implicaciones en la evolución de la falla de Crevillente (sector Abanilla-Alicante)

En este estudio presentamos los resultados del análisis estructural del borde norte de la cuenca del Bajo Segura, en la cordillera Bética oriental. En este borde se desarrolla el sinclinal de Crevillente; se trata de un pliegue de propagación de falla con geometría de crecimiento y vergente al sur asociado a la falla de Crevillente (sector Abanilla-Alicante). El estudio cuantitativo de la discordancia progresiva asociada a dicho pliegue ha puesto de manifiesto que la actividad de esta falla se inició en el Tortoniense, aumentó durante el Messiniense y, a partir de ese momento se ha mantenido constante o ha disminuido durante el Plioceno y el Cuaternario. La escasez de depósitos cuaternarios deformados no implica que no exista actividad cuaternaria de la falla de Crevillente (sector Abanilla-Alicante), ya que la mayoría de los depósitos más recientes son discontinuos o se localizan al sur, alejados de la zona de máxima deformación. Por otro lado, el hecho de que la actividad de la falla del Bajo Segura, situada en el borde meridional de la cuenca, se iniciara durante el Plioceno, parece indicar una migración de la deformación hacia el sur.

Water reduction in waste-activated sludge by resettling and filtration in batch. Phase (1): pilot-scale experiments to optimize performance

This article describes an effective procedure for reducing the water content of excess sludge production from a wastewater treatment plant by increasing its concentration and, as a consequence, minimizing the volume of sludge to be managed. It consists of a pre-dewatering sludge process, which is used as a preliminary step or alternative to the thickening. It is made up of two discontinuous sequential stages: the first is resettling and the second, filtration through a porous medium. The process is strictly physical, without any chemical additives or electromechanical equipment intervening. The experiment was carried out in a pilot-scale system, consisting of a column of sedimentation that incorporates a filter medium. Different sludge heights were tested over the filter to verify the influence of hydrostatic pressure on the various final concentrations of each stage. The results show that the initial sludge concentration may increase by more than 570% by the end of the process with the final volume of sludge being reduced in similar proportions and hydrostatic pressure having a limited effect on this final concentration. Moreover, the value of the hydrostatic pressure at which critical specific cake resistance is reached is established.

Simulating Granite Emplacement and Deformation with Centrifuge Analogue Modelling

The Greater Himalayan leucogranites are a discontinuous suite of intrusions emplaced in a thickened crust during the Miocene southward ductile extrusion of the Himalayan metamorphic core. Melt-induced weakening is thought to have played a critical role in strain localization that facilitated the extrusion. Recent advancements in centrifuge analogue modelling techniques allow for the replication of a broader range of crustal deformation behaviors, enhancing our understanding of large hot orogens. Polydimethylsiloxane (PDMS) is commonly used in centrifuge experiments to model weak melt zones. Difficulties in handling PDMS had, until now, limited its emplacement in models prior to any deformation. A new modelling technique has been developed where PDMS is emplaced into models that have been subjected to some shortening. This technique aims to better understand the effects of melt on strain localization and potential decoupling between structural levels within an evolving orogenic system. Models are subjected to an early stage of shortening, followed by the introduction of PDMS, and then a final stage of shortening. Theoretical percentages of partial melt and their effect on rock strength are considered when adding a specific percentage of PDMS in each model. Due to the limited size of the models, only PDMS sheets of 3 mm thickness were used, which varied in length and width. Within undeformed packages, minimal surface and internal deformation occurred when PDMS is emplaced in the lower layer of the model, showing a vertical volume increase of ~20% within the package; whereas the emplacement of PDMS into the middle layer showed internal dragging of the middle laminations into the lower layer and a vertical volume increase ~30%. Emplacement of PDMS results in ~7% shortening for undeformed and deformed models. Deformed models undergo ~20% additional shortening after two rounds of deformation. Strain localization and decoupling between units occur in deformed models where the degree of deformation changes based on the amount of partial melt present. Surface deformation visible by the formation of a bulge, mode 1 extension cracks and varying surface strain ellipses varies depending if PDMS is present. Better control during emplacement is exhibited when PDMS is added into cooler models, resulting in reduced internal deformation within the middle layer.