Irreversible inhibition of human cathepsins B, L, S and K by hypervalent tellurium compounds

The inhibition of human cysteine cathepsins B, L, S and K was evaluated by a set of hypervalent tellurium compounds (telluranes) comprising both organic and inorganic derivatives. All telluranes studied showed a time-and concentration-dependent irreversible inhibition of the cathepsins, and their second-order inactivation rate constants were determined. The organic derivatives were potent inhibitors of the cathepsins and clear specificities were detected, which were parallel to their known substrate specificities. In all cases, the activity of the tellurane-inhibited cathepsins was recovered by treatment of the inactivated enzymes with reducing agents. The maximum stoichiometry of the reaction between cysteine residues and telluranes were also determined. The presented data indicate that it is possible to design organic compounds with a tellurium(IV) moiety as a novel warhead that covalently modifies the catalytic cysteine, and which also form strong interactions with subsites of cathepsins B, L, S and K, resulting in more specific inhibition.

Proteomic analysis of dorsolateral prefrontal cortex indicates the involvement of cytoskeleton, oligodendrocyte, energy metabolism and new potential markers in schizophrenia

Schizophrenia is likely to be a consequence of serial alterations in a number of genes that, together with environmental factors, will lead to the establishment of the illness. The dorsolateral prefrontal cortex (Brodmann`s Area 46) is implicated in schizophrenia and executes high functions such as working memory, differentiation of conflicting thoughts, determination of right and wrong concepts, correct social behavior and personality expression. We performed a comparative proteome analysis using two-dimensional gel electrophoresis of pools from 9 schizophrenia and 7 healthy control patients` dorsolateral prefrontal cortex aiming to identify, by mass spectrometry, alterations in protein expression that could be related to the disease. In schizophrenia-derived samples, our analysis revealed 10 downregulated and 14 upregulated proteins. These included alterations previously implicated in schizophrenia, such as oligodendrocyte-related proteins (myelin basic protein and transferrin), as well as malate dehydrogenase, aconitase, ATP synthase subunits and cytoskeleton-related proteins. Also, six new putative disease markers were identified, including energy metabolism, cytoskeleton and cell signaling proteins. Our data not only reinforces the involvement of proteins previously implicated in schizophrenia, but also suggests new markers, providing further information to foster the comprehension of this important disease. (C) 2008 Elsevier Ltd. All rights reserved.

Proteome analysis of human dorsolateral prefrontal cortex using shotgun mass spectrometry

The prefrontal cortex executes important functions such as differentiation of conflicting thoughts, correct social behavior and personality expression, and is directly implicated in different neurodegenerative diseases. We performed a shotgun proteome analysis that included IEF fractionation, RP-LC, and MALDI-TOF/TOF mass spectrometric analysis of tryptic digests from a pool of seven human dorsolateral prefrontal cortex protein extracts. In this report, we present a catalog of 387 proteins expressed in these samples, identified by two or more peptides and high confidence search scores. These proteins are involved in different biological processes such as cell growth and/or maintenance, metabolism/energy pathways, cell communication/signal trarisduction, protein metabolism, transport, regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism, and immune response. This analysis contributes to the knowledge of the human brain proteome by adding sample diversity and protein expression data from an alternative technical approach. It will also aid comparative studies of different brain areas and medical conditions, with future applications in basic and clinical research.

Voltammetric characterization of stepped platinum single crystal surfaces vicinal to the (110) pole

Platinum stepped surfaces vicinal to the (1 1 0) crystallographic pole have been investigated voltammetrically in 0.1 M HClO(4) and 0.1 M H(2)SO(4) solutions. Changes in the voltammetric profile with the step density suggest the existence of two types of surface sites, that has been ascribed to linear and bidimensional domains. This result indicates the existence of important restructuring processes that separate the real surface distribution from the nominal one. The electronic properties of the surfaces have been characterized with the CO charge displacement method and the potential of zero total charge has been calculated as a function of the step density. (c) 2009 Elsevier B.V. All rights reserved.

Vernacular meaning making : Examples of narrative impact in fiction film questioning the 'banal' notion in mediatization of religion theory

The outcome of an audience study supports theories stating that stories are a primary means by which we make sense of our experiences over time. Empirical examples of narrative impact are presented in which specific fiction film scenes condense spectators' lives, identities and beliefs. One conclusion is that spectators test the emotional realism of the narative for greater significance, connecting diegetic fiction experiences with their extra-diegetic world in their quest for meaning, self and identity. The 'banal' notion of the mediatization of religion theory is questioned as unsatisfactory in the theoretical context of individualized meaning-making processes. As a semantically negatively charged concept, it is problematic when analyzing empirical examples of spectators' use of fictional narratives, especially when trying to characterize the idiosyncratic and complex interplay between spectators' fiction emotions and their testing of mediated narratives in an exercise to find moral significance in extra-filmic life. Instead vernacular meaning-making is proposed.

Topic- and mode-sensitive interaction strategies : Functions of ellipsis in oral communication

In this article, we discuss ellipsis as an interactive strategy by analysing the author’s textchat corpus and the VOICE corpus of English as a Lingua Franca. It is found that there were fewer repetitions in the textchat data, and this is explained as a consequence of the textchat mode. Textchat contributions are preserved as long as the chat is active or has been saved, and therefore users can scroll through and review the discussion, compared to the more fleeting nature of oral conversation. As a result, repetition is less necessary. The frequency of other functions identified could be attributed to the topic of discourse. Discussions involve much ellipsis used to develop discourse, although some were self-presentations with repetition used to confirm details. Back-channel support and comments were often low because speakers instead used forms like yeah as supportive utterances.

The use of software Mapavox for teaching graphics and games to blind and low vision students: a development through practices

Current policies on education to visually impaired point for a growing trend of including students with special educational needs in regular schools. However, most often this inclusion is not accompanied by an appropriate professional trained or infrastructure, which has been presented as a big problem for regular school teachers who have students with visual impairments in their classroom. Based on this situation, the Group of Extension in Tactile Cartography from UNESP - University of the State of São Paulo - Campus de Rio Claro - SP - Brazil has been developing educational material of geography and cartography to blind students at a special school. Among the materials developed in this study highlight the development of graphics and board games provided with sound capabilities through MAPAVOX, software developed in partnership with UFRJ - Federal University from Rio de Janeiro - RJ - Brazil. Through this software, sound capabilities can be inserted into built materials, giving them a multi-sensory character. In most cases the necessary conditions for building specific materials to students with visual impairments is expensive and beyond the reach of features from a regular school, so the survey sought to use easy access and low cost materials like Cork, leaf aluminum, material for fixing and others. The development of these materials was supported by preparation in laboratory and its subsequent test through practices involving blind students. The methodology used on the survey is based on qualitative research and non comparative analysis of the results. In other words, the material is built based on the special students perception and reality construction, not being mere adaptations of visual materials, but a construction focused on the reality of the visually impaired. The results proved were quite successful as the materials prepared were effective on mediating the learning process of students with disabilities. Geographical and cartographic concepts were seized by the students through the technology used, associated with the use of materials that took into account in its building process the perception of the students.

Estimates of genetic correlations between days to calving and reproductive and weight traits in Nelore cattle

Data comprising 53,181 calving records were analyzed to estimate the genetic correlation between days to calving (DC), and days to first calving (DFC), and the following traits: scrotal circumference (SC), age at first calving (AFC), and weight adjusted for 550 d of age (W550) in a Nelore herd. (Co)variance components were estimated using the REML method fitting bivariate animal models. The fixed effects considered for DC were contemporary group, month of last calving, and age at breeding season (linear and quadratic effects). Contemporary groups were composed by herd, year, season, and management group at birth; herd and management group at weaning; herd, season, and management group at mating; and sex of calf and mating type (multiple sires, single sire, or AI). In DFC analysis, the same fixed effects were considered excluding the month of last calving. For DC, a repeatability animal model was applied. Noncalvers were not considered in analyses because an attempt to include them, attributing a penalty, did not improve the identification of genetic differences between animals. Heritability estimates ranged from 0.04 to 0.06 for DC, from 0.06 to 0.13 for DFC, from 0.42 to 0.44 for SC, from 0.06 to 0.08 for AFC, and was 0.30 for W550. The genetic correlation estimated between DC and SC was low and negative (-0.10), between DC and AFC was high and positive (0.76), and between DC and W550 was almost null (0.07). Similar results were found for genetic correlation estimates between DFC and SC (-0.14), AFC (0.94), and W550 (-0.02). The genetic correlation estimates indicate that the use of DC in the selection of beef cattle may promote favorable correlated responses to age at first mating and, consequently, higher gains in sexual precocity can be expected.

Effects of scrotal insulation in Nellore bulls (Bos taurus indicus) on seminal quality and its relationship with in vitro fertilizing ability

The objectives of this study were to assess the effects of induced testicular degeneration in Bos taurus indicus (Nellore) bulls on changes in seminal characteristics and fertilizing ability of sperm. Four Nellore bulls (30-36-month-old, 500-550 kg) with good seminal quality (> 80% motile and morphologically normal sperm) had serotal insulation applied for 5 d. Semen was collected by electroejaculation and cryopreserved at a the pre-insulation moment, and 7, 14, and 21 d after insulation was removed. Gross motility, vigor of sperm movement (1-5), acrosome integrity, sperm morphology (phase-contrast microscopy), nuclear vacuoles and abnormal chromatin (Feulgen-stain) were determined after sperm preparations for in vitro fertilization (IVF). Prior to IVF, sperm were separated using a Percoll gradient (45% and 90%). Normal sperm decreased (P < 0.05) 14 and 21 d after insulation was removed. on 14 and 21 d, the incidence of head defects (9.7 +/- 0.6 and 17.0 +/- 0.8, respectively; mean +/- S.E.M) was higher (P < 0.05) in agreement with the incidence of nuclear vauoles (14.0 +/- 5.0 and 12.3 +/- 2.3) and abnormal chromatin (24.4 +/- 7.2 and 30.8 +/- 2.8). Although the frequency of cleaved oocytes decreased only on 21 d (P < 0.05), blastocyst rates were lower (P < 0.05) than pre-insulation on 14 and 21 d. In regression analyses, only nuclear vacuoles, head defects and intact acrosome accounted for differences in cleavage (R(2) = 0.38, 0.48, and 0.30, respectively) and blastocyst rates (R(2) = 0.35, 0.37, and 0.44). Abnormal chromatin was associated only with blastocyst rates (R(2) = 0.35). In conclusion, blastocyst rate was more sensitive than cleavage rate and the assessment of nuclear integrity is recommended to predict the fertilizing ability of bull sperm. (c) 2008 Elsevier B.V. All rights reserved.

Yield of upland rice cultivars in rainfed and sprinkler-irrigated systems in the Cerrado region of Brazil

In upland rice, the reduced grain yield that originates from the moisture stress period is related to the plant's tolerance of water deficiency and may vary between cultivars. The purpose of the work presented here was to evaluate the performance of upland rice cultivars in both rainfed and sprinkler-irrigated systems. A split-plot scheme with 8 replicates in a randomised block design was used. The plots were composed of 2 cropping systems (rainfed and sprinkler-irrigated) and the split-plot consisted of 2 cultivars (IAC 201 and Carajas) which are suggested for cultivation in upland ecosystems. Carajas had a greater number of panicles per square metre, higher spikelet fertility and grain mass, and, consequently, a higher grain yield than IAC 201 regardless of cropping system. IAC 201 was more sensitive to water deficiency than Carajas. Sprinkler irrigation improved spikelet fertility, grain mass and upland rice grain yield. Even when cultivars with a higher tolerance of water deficiency are used, a sprinkler-irrigated system may be a viable method to increase upland rice yield throughout most of the Brazilian Cerrado.

Growth Regulation and Other Secondary Effects of Herbicides

As all herbicides act on pathways or processes crucial to plants, in an inhibitory or stimulatory way, low doses of any herbicide might be used to beneficially modulate plant growth, development, or composition. Glyphosate, the most used herbicide in the world, is widely applied at low rates to ripen sugarcane. Low rates of glyphosate also can stimulate plant growth (this effect is called hormesis). When applied at recommended rates for weed control, glyphosate can inhibit rust diseases in glyphosate-resistant wheat and soybean. Fluridone blocks carotenoid biosynthesis by inhibition of phytoene desaturase and is effective in reducing the production of abscisic acid in drought-stressed plants. Among the acetolactate synthase inhibitors, sulfometuron-methyl is widely used to ripen sugarcane and imidazolinones can be used to suppress turf species growth. The application of protoporphyrinogen oxidase inhibitors can trigger plant defenses against pathogens. Glufosinate, a glutamine syntherase inhibitor, is also known to improve the control of plant diseases. Auxin agonists (i.e., dicamba and 2,4-D) are effective, low-cost plant growth regulators. Currently, auxin agonists are still used in tissue cultures to induce somatic embryogenesis and to control fruit ripening, to reduce drop of fruits, to enlarge fruit size, or to extend the harvest period in citrus orchards. At low doses, triazine herbicides stimulate growth through beneficial effects on nitrogen metabolism and through auxin-like effects. Thus, sublethal doses of several herbicides have applications other than weed control.