Top PDF Timing the generation of distinct retinal cells by homeobox proteins.

Timing the generation of distinct retinal cells by homeobox proteins.

Timing the generation of distinct retinal cells by homeobox proteins.

The inhibition of GFP translation driven by these UTRs in specific cell types is statistically significant, as reported in Figure 3B. Recently, extensive bioinformatic analyses have shown that at least 20% of the vertebrate genes display in their 39 UTR a family of highly conserved short regions [25], most of which are complementary to a newly discovered class of regulatory short RNAs called microRNAs (miRNAs). Accordingly, cis-acting signals controlling protein translation through the binding of a miRNA have been found in the 39 untranslated region (UTR) of Hox genes [26]. Using an in silico approach, we found that the 39 UTR of Xotx5b, Xvsx1, and Xotx2 contains candidate miRNA domains for 42 distinct miRNAs, four of which are shared by all the three 39 UTRs (Table S1). These miRNA domains are widely dispersed in the 39 UTR of each gene. Whereas such miRNA domains could reveal a functional relevance, specific RNA-binding proteins might also be involved in regulating the translation of retinal Figure 1. The Xenopus Xvsx1 Homeobox Gene Supports Bipolar Cell Fate (A–C) Sections of st. 42-lipofected retinas. GFP (green) traces lipofection. (A) Example of control lipofection. (B and C) Example of Xvsx1 lipofection. (C) Immunostaining (red fluorescence) with amacrine antibodies panel (anti-5-HT, anti-GABA, anti-tyrosine hydroxilase), labeling the main classes of amacrine cells at this developmental time [47,48] ONL: outer nuclear layer; INL: inner nuclear layer; GCL: ganglion cell layer. Xvsx1 lipofection (B) increases the proportion of INL cells and decreases the proportion of ONL cells compared to control (A). The majority of the Xvsx1-lipofected cells in the INL are not stained either by amacrine markers (C), or by the horizontal marker prox1 (not shown).
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Modulation of Drosophila retinal epithelial integrity by the adhesion proteins capricious and tartan.

Modulation of Drosophila retinal epithelial integrity by the adhesion proteins capricious and tartan.

acting to organise epithelial packing. Detailed inspection of cells in the furrow and immediately after they emerge from it, shows profound rearrangement that starts with straight lines of cells, evolving into arcs and finally into morphologically distinct clusters [4]. Adhesion defects in the furrow may disrupt this process such that ommatidial clusters and their spacing become less ordered. We do not understand why these phenotypes only manifest at clone boundaries, but we presume it is a consequence of a discontinuity in adhesive properties. Similarly, the short range non-autonomy of the phenotype is probably due to local cell packing problems caused by adhesion anomalies at the boundaries of wild-type and mutant tissue. Another possible explanation for the non-autonomous effects is that changes in cell shape and epithelial morphology in the furrow could affect the range or efficiency of intercellular signalling molecules, thereby affecting normal retinal development. Little is known about how epithelial characteristics can modulate secreted signals and this will be a fruitful area for future study.
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Retinal pigment epithelium degeneration caused by aggregation of PRPF31 and the role of HSP70 family of proteins

Retinal pigment epithelium degeneration caused by aggregation of PRPF31 and the role of HSP70 family of proteins

To explore the role of Hsp70 family in the RPE affected by a p.A216P mutation, we overexpressed both WT PRPF31 and mutant A216P tagged to GFP in a human- derived RPE cell line (ARPE-19). Immunofluorescence staining results are in line with the in vivo results, with WT PRPF31-GFP protein being located mainly in the nu- cleus, and mutant A216P-GFP protein being mostly aggre- gated in the cytoplasm. By Western blot analysis we found that cells overexpressing the mutant variant have a signifi- cant decrease in the soluble fraction of PRPF31 and an in- crease in the insoluble PRPF31 protein. Moreover, the overexpression of the mutant protein leads to a depletion of the soluble endogenous PRPF31 protein and WT PRPF31 tagged to Flag as well, suggesting a dominant- negative effect. These results are in accordance with one of the mechanisms proposed by Yin and coworkers in which they report that mutations in PRPF31 can induce retinal degeneration (Yin et al., 2011). They proposed three mechanisms: i) haploinsufficiency due to loss of function of the mutant protein or degradation of mutant mRNA by nonsense-mediated mRNA decay, thus com- promising the splicing machinery; ii) mutant proteins with dominant-negative activity that may interfere with splicing and potentially with other cellular activities, leading to de- generation of the affected tissue; and iii) mutations might promote proteins forming insoluble and cytotoxic aggre- gates that can affect the tissue by loss-of-function and dominant-negative effects (Yin et al., 2011). We also ob- served that Hsp70 was upregulated in the cells overex- pressing A216P-GFP and colocalized with PRPF31 mutant protein. These results corroborate our in vivo findings of Hspa4l upregulation in the RPE of Prpf31 A216P/+ mice and its colocalization with PRPF31 protein aggregates.
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The comparison of the structure and microhardness of the tool steel C90 and HS 6-5-2 remelted with the electric arc

The comparison of the structure and microhardness of the tool steel C90 and HS 6-5-2 remelted with the electric arc

Machine and tools elements made of the steel C90 and HS 6-5-2 immediately after the conventional hardening, need the tempering process. During the tempering, there is a transforma- tion of retained austenite into martensite and carbides release in martensite, what leads to the increase hardness of the high-speed steel, whereas in non-alloy steels tempering cause decrease the hardness.

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SOCIAL ECONOMY – A FORM OF INCLUSION AND OF ''REACTIVATING'' OF LABOR IN THE CONTEXT OF THE CURRENT CRISIS

SOCIAL ECONOMY – A FORM OF INCLUSION AND OF ''REACTIVATING'' OF LABOR IN THE CONTEXT OF THE CURRENT CRISIS

)n the context of the cohesion policy, solidarity must represent a support for development . For that purpose, solidarity can be seen as a help for self‐help and its success depends a great deal on the capacity and the training of the people to whom the support of making maximum profit out of these addresses to. This support does not mean exclusively financial support, although it is necessary and important but, of all things, it means an exchange of experiences and cooperation, the development of capacity through training, open discussions with the interested factors and last but not least a critic, but a constructive dialogue between the various levels of government: European, national, regional, local. )n other words, a functional labor market should represent a catalyst for the general objective of the European Union – social and economical cohesion – because it has in view the connections with the different markets of the services and of the goods and generates the necessary income for supporting the participation of the individuals, bringing them together, placing them in collaborations. )n this context, the starting points for promoting the inclusion through the activities of social economy have in view: adapting the institutional environment, developing the public‐private partnership, developing the social dialogue between players, investments in the human capital and supporting the exchange of good practices within the European Union.
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Timing and mechanisms for the generation and modification of the anomalous topography of the Borborema Province, northeastern Brazil

Timing and mechanisms for the generation and modification of the anomalous topography of the Borborema Province, northeastern Brazil

The results of apatite fission-track analysis in 14 granitic-gneissic samples from two regional transects across the Borborema Plateau, northeastern Brazil, show evidence for two dominant paleothermal events: a Late Cretaceous cooling event beginning sometime between 100 and 90 Ma, and a second cooling event in the Neogene. The distribution of the fission-track results suggests that the cooling events have a broad regional expression and are consistent with the geologic record in the Araripe Basin, western Borborema Province, which attests to a post-Albian uplift of the whole region. We hypothesize that the first event is due to the uplift and denudation of regional, permanent topography generated after the breakup of Brazil and Africa. Such topography is predicted by models of continental margin extension in which continental lithosphere thinning is followed by thickening of the adjacent hinterland litho- sphere and crust (Kusznir, N.J., Karner, G.D., 2007. Continental lithospheric thinning and breakup in response to upwelling divergent mantle flow: application to the Woodlark, Newfoundland and Iberia margins. In: Karner, G.D., Manatschal, G., Pinheiro, L. (Eds), Imaging, mapping and modeling continental lithosphere extension and breakup. Special Publication 282, Geological Society, London, pp. 389–419.). In northeastern Brazil, this extension-engendered topography may have been amplified by magmatic underplating related to the Saint Helena and Ascension plumes. The Miocene cooling event (20–0 Ma) occurred at a time characterized by the transition from carbonate ramp to progradational clastic systems on the Pernambuco–Paraı´ba margin and the offshore Potiguar Basin. This same stratigraphic response characterizes the Neogene stratigraphy of many passive margins and attests to a global increase in the delivery of clastics to margins, the simplest explanation of which is a climate change that accentuated erosion of pre-existing topography. Thus, the present rugged landscape of northeastern Brazil is inter- preted to be a product of this younger denudation event. A corollary of this study is that the history, distribution and delivery of clastics to the northern and northeastern margins of Brazil are a function of the regional development of the continental landscape during the Late Cenozoic.
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Biophysical modulation of cell fate through chromatin remodelling

Biophysical modulation of cell fate through chromatin remodelling

27 The chromatin state is determined by the DNA and histone modifications on the nucleosome particle, which include DNA methylation and histone acetylation, methylation, phosphorylation, ubiquitination and sumoylation (Martins et al., 2012). A very interesting feature related with DNA methylation has to do with the possible effect of hydration of the DNA molecules in the chromatin packaging process (Kaur et al., 2012). In the presence of water, chromatin reconstituted on methylated DNA is more compact due to the methyl group hydrophobicity that favours a stiffer DNA molecular conformation (A DNA) (Kaur et al., 2012). This effect is less noticeable when performing the same experiments with unmethylated DNA. These displacement water forces also play a role in the DNA interface with proteins like histone proteins, ligases and eventually the control over the access of TFs (Kaur et al., 2012). This hydration mechanism might be also playing a role in the regulation of CpG islands. These regions, are DNA sites in which the frequency of the cytosine (C) and guanine (G) nucleotide sequence is higher than other regions, they typically occur at or near the transcription start site of genes and regulate the transcriptional activity of those genes (Illingworth and Bird, 2009). The binding of TFs to these promoter regions is regulated by methylation of the CpG sequences. Also, the interaction of specific TFs and the DNA binding sequence is influenced by the presence of osmolytes and hydration of the DNA molecule. The early growth response protein 1 (EGR1), a zinc finger protein TF also known as Zif268, is subject of interactions with osmolytes which stabilise the conformational structure of the unbound EGR1 in detriment of the DNA-bound EGR1 conformational state (Mikles et al., 2015). On the other hand, PU.1 is a pioneer TF important for myeloid differentiation. It shows preferential hydration in sequence discrimination in a different way from what happens with other E-twenty six (Ets) TF family members such as Ets-1. Interestingly, PU.1 activity is critical to the development and function of macrophages and lymphocytes, which present osmotically variable environments, and hydration-dependent specificity of transcription binding may represent an important in vivo regulatory mechanism. A hypothesis which supports gene expression profiles of primary murine macrophages (Poon, 2012; Wang et al., 2014). The mechanism of regulation of binding affinity by DNA hydration for Ets-1 and PU.1 is schematized in Figure 1.14 and hypothesises the water dependence of PU.1 to identify its binding site and promotes the formation of high-affinity binding complexes between the TF and the DNA. This effect is no longer observed in the binding mechanism of Ets-1 to the DNA target sites (Poon, 2012; Wang et al., 2014).
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O núcleo supraquiasmático e o folheto intergenicula do do morcego (Artibeus planirostris): projeção retiniana e caracterização neuroquímica

O núcleo supraquiasmático e o folheto intergenicula do do morcego (Artibeus planirostris): projeção retiniana e caracterização neuroquímica

The circadian timing system (CTS) comprises a set of neural structures that include input pathways, such retinal projections, which allow the synchronization of the biological rhythms to environmental cycles; a central circadian pacemaker, which generates the circadian signal and output pathways connecting the pacemaker to the behavioral effectors. Among the major components of the STC, highlight the suprachiasmatic nucleus (SCN), classically known as the neural structure that governs biological rhythmicity, and the intergeniculate leaflet (FIG) of the thalamic lateral geniculate complex, modulator pacemaker. In this study, both circadian centers were evaluated in respect to their cytoarchiteture, pattern of the retinal innervations and chemical content with a Nissl stain, neural tracer and imunohistochemical techniques in bat Artibeus planirostris, common microchiropteran in Brazil. Based on these techniques was observed in rostral sections, the SCN had an approximately triangular shape and in middle and caudal sections, this nucleus assumed an ellipsoidal contour. It receives bilateral retinal innervations, with discrete contralateral predominance and contains vasopressin (VP), vasoactive intestinal polypeptide (VIP), calbindin (CB) e calretinin (CR) immunoreactive cell bodies; neuropeptide Y (NPY) and serotonin (5-HT) imunopositive fibers/terminals, besides to glial fibrillary acidic protein (GFAP) labeling. The IGL contains NPY, CB and CR immunoreactive perikarya and receives a bilateral retinal projection. The rostral and middle IGL had a leaflet shape between the DLG and VLG. At a caudal level it had a descending portions which outlines de VLG medially. This is the first report examining the CTS of these species of chiropteran. The results indicate that retinal input and chemical content of the SCN and IGL in Artibeus planirostris are similar other mammalian species. In contrast, the SCN of these bat transcend the classical organizational schemes proposed in the scientific literature. Hodological and molecular studies are needed to stablish a specific division of this structure in these species of chiropteran
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Modulation of the expression of the transcription factor Max in rat retinal ganglion cells by a recombinant adeno-associated viral vector

Modulation of the expression of the transcription factor Max in rat retinal ganglion cells by a recombinant adeno-associated viral vector

tion factor Max, which is found mostly within the nucleus of normal cells, undergoes ex- clusion from the nucleus early upon induc- tion of programmed cell death in retinal ganglion cells, followed by complete loss of Max immunoreactivity as apoptotic cell death proceeds (5). The early nuclear exclusion of Max probably leads to the loss of its tran- scriptional regulatory activity, which may be an early and necessary step for the execution of cell death (5). Max is ubiquitously ex- pressed and its absence leads to early embry- onic lethality (6). It has been shown that the selective over-expression of Max in endo- thelial cells blocks apoptosis promoted by serum withdrawal (7), suggesting a cell pro- tective function for this protein. If, indeed, the early loss of nuclear Max reduces neuro- protection, then its overexpression might counteract the retrograde degeneration of retinal ganglion cells following axon dam- age. Modulation of gene expression is, how- ever, notoriously difficult in postmitotic, dif- ferentiated neurons. This article describes a technique successfully used to modulate the expression of Max in retinal ganglion cells, together with preliminary results indicating a decrease in the sensitivity of transduced neurons to retrograde degeneration.
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Co-expression of two subtypes of melatonin receptor on rat M1-type intrinsically photosensitive retinal ganglion cells.

Co-expression of two subtypes of melatonin receptor on rat M1-type intrinsically photosensitive retinal ganglion cells.

excitability of these cells, including resting potentials [57,58], membrane conductances [59], and multiple types of membrane channels [60,61] etc., and/or synaptic transmission [61,62]. In rats, melatonin potentiates inputs from glycinergic amacrine cells to RGCs [25]. For ipRGCs, melatonin may modulate, just like at any conventional RGCs, synaptic input from bipolar and amacrine cells [63,64]. Alternatively, activation of melatonin receptors in these cells may di- rectly intervene with the melanopsin phototransduction cascade. For example, melanopsin lev- els may be regulated by melatonin. It is also possible that some effectors of melatonin receptor activation, such as PLC and PKC, may be key components of the melanopsin cascade [65,66]. In addition, multiple phosphorylation sites melanopsin possesses [42,67] may also be the sub- strates of some kinases at the downstream of melatonin receptor activation. Melatonin may di- rectly be involved in modulation of ipRGC activity by activating MT 1 and MT 2 receptors in
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The modification process of AlSi21CuNi silumin and its effect on change of mechanical properties of the alloy

The modification process of AlSi21CuNi silumin and its effect on change of mechanical properties of the alloy

Considering mechanism of modification of these precipitations one should take into account that effect of modification of hypereutectic silumins depends on earlier transition to liquid phase of sparingly soluble crystals of primary silicon [1-3]. Tests performed by authors of the studies [4-10] enable utilization of modification treatments together with making use of a various micro additives in order to improve properties of hypereutectoid alloys.

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Rif1 regulates initiation timing of late replication origins throughout the S. cerevisiae genome.

Rif1 regulates initiation timing of late replication origins throughout the S. cerevisiae genome.

origins in subtelomeric as well as internal chromosomal loci, while also delaying or repressing the activation of normally early origins, including pericentric origins [15]. The effects of Rif1 deletion in mouse cells or depletion in human cells appear to be similar to those in fission yeast, with advanced timing of late domains together with delayed replication of early domains resulting in an overall compression of the temporal replication program [14,16]. Analysis of budding yeast rif1D cells showed advanced replication timing of subtelomeric regions, relative to an internal early and an internal late origin, suggesting that origin regulation by Rif1 in budding yeast might be limited to subtelomeric domains [17]. However, these data also appear to indicate that the internal early origin used as a standard (ARS1) was delayed, and happens to reside near a centromere, consistent with the possibility that early origin timing, particularly of pericentric regions, is regulated by Rif1 in budding yeast as in fission yeast. This might also explain how pericentric origins remain early-firing in the absence of transcription factors Fkh1 and Fkh2, which are required for early- firing of most non-pericentric early origins in budding yeast [12]. The mechanism of Rif1 function in origin regulation also requires further elucidation. Rif1 regulates telomere length, which has been implicated in the control of telomere replication timing in S. cerevisiae (reviewed in [21]). Thus, Rif1’s effect on subtelomeric replication timing has been attributed to its function in controlling telomere length. However, this mechanism does not easily account for effects of Rif1 at internal chromosomal loci as observed in S. pombe [15]. In both yeasts, Rif1 binds internal chromosomal loci independently of its telomere-binding partner Rap1 or Taz1, although the significance of this binding has not been carefully examined [15,22]. Rif1 may perform a scaffolding function to organize or localize chromatin domains. In mammalian cells, Rif1 fractionates with the insoluble nuclear scaffold, and the structure of Rif1 (in yeast and mammals) contains motifs that mediated protein-protein interaction, consistent with a scaffolding function [14,16,23]. In S. cerevisiae, palmitoylation of Rif1 is required for localization of telomeres to the nuclear periphery, which is typically associated with late replication [24]. Thus, Rif1’s function in telomere localization may contribute to its role in origin timing, at least in yeast. Whether Rif1 plays a similar function to localize internal chromosomal loci to the nuclear periphery remains to be determined.
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Operating characteristics of turbine mixers based on the analysis of power demand of the mixer’s drive

Operating characteristics of turbine mixers based on the analysis of power demand of the mixer’s drive

Optimisation of the turbine mixer’s performance during the preparations of the sand mix still remains an important issue as this mixer type is now in widespread use. Monitoring techniques of the system sand mixing include the analysis of electric power demand by the mixer’s drive based on measurements of power components. This study shows the operating characteristics of turbine mixers as the function of electric power demand by the drive system.

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Bioactive form of resveratrol in glioblastoma cells and its safety for normal brain cells

Bioactive form of resveratrol in glioblastoma cells and its safety for normal brain cells

Resveratrol, a plant polyphenol existing in grapes and many other natural foods [3], possesses a wide range of biological activities including cancer prevention [4,5]. More importantly, resveratrol has little cytotoxic effect and is able to penetrate blood-brain barrier [6], suggesting its potential therapeutic values in the management of glioblastoma. It has been recognized that resveratrol is intracellularly biotransformed to different metabolites, but no direct evidence has been available to ascertain its bioactivity form, and how normal brain cells respond to this agent. So it would be worthwhile to identify the real biological form of trans-resveratrol and e valuate the resveratrol’s safety in the normal glial cells with effective anticancer dose.
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Evaluation of early abnormalities of the sensory retina in a hypercholesterolemia experimental model: an immunohistochemical study

Evaluation of early abnormalities of the sensory retina in a hypercholesterolemia experimental model: an immunohistochemical study

Finally it is important to point out that early retinal alte- rations induced by hypercholesterolemia, mainly the ones related to inner retinal layers, have not been studied scien- tifically until the present time. This study seeks to contri- bute to the elucidation of the physiopathology of the ma- cular degenerative disease induced by an increase in the seric cholesterol. Consequently, the authors stress the im- portance of the cardiovascular control of the atherosclerotic disease as an attempt to avoid or reduce the macular damage.
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The homeobox gene Gsx2 regulates the self-renewal and differentiation of neural stem cells and the cell fate of postnatal progenitors.

The homeobox gene Gsx2 regulates the self-renewal and differentiation of neural stem cells and the cell fate of postnatal progenitors.

Infection was achieved using a Moloney murine leukaemia virus-based retroviral vector (RetrofectH: Cellerix S.L, Madrid [2]). The retroviral construct pRV-IRES-EGFP (referred to simply as the EGFP vector) was used as a control in infection experiments. The human Gsx2 ORF (1 Kb) was amplified from a pcDNA-Gsh2 plasmid [31] by PCR using specific 59 and 39 primers containing BamHI and XhoI restriction sites (sense primer: 59-TTG GGA TCC ACC ATG TCG CGC TCC TTC TAT G-39; antisense primer: 59-TTC CTC GAG TCA TAA GGG GGA AAT CTC CTT-3 9). The PCR fragment amplified was cloned into the pRV-IRES-EGFP vector and then sequenced. A clone was selected in which there were no mutations in the coding region and this was then used to generate viral particles by transfecting it into 293T HEK cells. The titers obtained were in the range of 10 5 –10 6 infection units (IU)/ml, as measured by
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Conditioned medium from activated spleen cells supports the survival of rat retinal cells in vitro

Conditioned medium from activated spleen cells supports the survival of rat retinal cells in vitro

Cytokines are a heterogeneous group of molecules that have been associated with several functions in the nervous system, such as survival and differentiation of neuronal and glial cells. In the present study, we demonstrated that conditioned medium from spleen cells activated with concanavalin A increased neuritogenesis and survival of retinal cells, as measured by biochemical and morphological crite- ria. Our data showed that conditioned medium induced a five-fold increase in the amount of protein after 120 h in vitro. This effect was not inhibited by the blockade of voltage-dependent L-type calcium channels with 5.0 µM nifedipine. However, the use of an intracellular calcium chelator (15.0 µM BAPTA-AM) inhibited this effect. Our results support the idea that factors secreted by activated lymphocytes, such as cytokines, can modulate the maintenance and the differentia- tion of rat retinal cells in vitro, indicating a possible role of these molecules in the development of retinal cells, as well as in its protec- tion against pathological conditions.
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Morphology of the male reproductive system and spermiogenesis in Hypanthidium foveolatum (Alfken, 1930) (Hymenoptera: Apidae: Megachilinae)

Morphology of the male reproductive system and spermiogenesis in Hypanthidium foveolatum (Alfken, 1930) (Hymenoptera: Apidae: Megachilinae)

The morphological aspects of male reproductive tract, spermiogenesis and spermatozoa are typical for each species and reflect its evolution, establishing a unique source of characters, which has been used to help solve phylogenetic problems. In Hypanthidium foveolatum the reproductive tract is composed of the testes comprising 28 testicular tubules, deferent ducts, seminal vesicles, accessory glands and an ejaculatory duct. The differentiation of spermatids occurs within cysts of up to 128 germ line cells each one. During the early spermatid phase, the nucleus resembles that of somatic cells. There follows a gradual chromatin condensation with an increase in nuclear electron density. In the spermatozoon, the nucleus contains heterogeneous chromatin with a loose appearance. The acrosome, shaped with the active participation of the Golgi complex, shows an electron-dense perforatorium involved by four electron-lucent acrosomal vesicle projections. The sperm tail presents an axoneme with a 9 + 9 + 2 microtubule pattern and two mitochondrial derivatives, which appear with different sizes. A dense crystalloid is formed initially in the mitochondrial matrix of the large derivative. The mitochondrial derivatives’ differentiation occurs concomitantly with an axoneme outgrowth. The centriolar adjunct is observed near the axoneme, anterior to the smaller mithocondrial derivative and exhibits an approximately triangular shape in cross-sections. Microtubules were observed around the head region and flagellar components during spermiogenesis.
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J. bras. pneumol.  vol.36 número3 en v36n3a15

J. bras. pneumol. vol.36 número3 en v36n3a15

Although mechanical ventilation is an important therapy, it can result in complications. One major complication is ventilator-induced lung injury, which is caused by alveolar hyperdistension, leading to an inflammatory process, with neutrophilic infiltration, hyaline membrane formation, fibrogenesis and impaired gas exchange. In this process, cellular mechanotransduction of the overstretching stimulus is mediated by means of the cytoskeleton and its cell-cell and cell-extracellular matrix interactions, in such a way that the mechanical stimulus of ventilation is translated into an intracellular biochemical signal, inducing endothelial activation, pulmonary vascular permeability, leukocyte chemotaxis, cytokine production and, possibly, distal organ failure. Clinical studies have shown the relationship between pulmonary distension and mortality in patients with ventilator-induced lung injury. However, although the cytoskeleton plays a fundamental role in the pathogenesis of ventilator-induced lung injury, there have been few in vivo studies of alterations in the cytoskeleton and in cytoskeleton-associated proteins during this pathological process.
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Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology.

Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology.

Our results have several implications for the interpretation of genome-wide association studies: first, our ability to connect the majority of associated loci in a limited number of molecular networks suggests that these represent processes underlying pathogenesis. Second, these networks are unbiased, in the sense that they do not rely on previous classifications of gene function or pathway lists; rather, we assemble our networks from low-level functional genomics data and allow network structure, if any, to emerge. Third, our approach is general; we have demonstrated it using interactions between protein products, but any relationship between genes or other genomic features (non-coding RNAs, enhancer elements, conserved regions etc.) may be used in the same fashion. Even more powerful, approaches combining such orthogonal data types will be rewarding. The limitation to using PPI data from a curated database such as InWeb is that proteins for which no high-confidence interactions exist will be left out of the analysis. As such, our analysis is limited to proteins present in the database. Additionally, while we controlled for the biases we observed, other undetected biases still may exist.
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