Top PDF A human-specific de novo protein-coding gene associated with human brain functions.

A human-specific de novo protein-coding gene associated with human brain functions.

A human-specific de novo protein-coding gene associated with human brain functions.

However, protein-coding potential of FLJ33706 suggested by population genetics analysis was still not conclusive. To explore whether or not FLJ33706 actually encodes the 194-codon protein, we developed FLJ33706-specific antibody and performed Western blot analyses. We designed a 17-amino-acid antigenic peptide, CTSKAQRVHPQPSHQRQ, corresponding to the non-repeti- tive region (residues 68–83) of the FLJ33706 putative protein plus a cystine at the N-terminus to facilitate conjugation to an adjuvant. The epitope sequence had no homology with the coding peptides of Alu or other repeat elements and could not match any other proteins in NCBI NR database [20]. This peptide was synthesized Figure 1. Gene structure of FLJ33706 , a human-specific de novo protein-coding gene. Data for the tracks ‘Spliced Human EST’ and ‘Human mRNA’ was extracted and assembled from UCSC Genome Browser. We re-sequenced all available mRNAs and spliced ESTs, shown in the track ‘Re- sequenced ESTs/mRNAs’. On the basis of these data, we inferred gene structure for this novel gene, with six exons marked as ‘1,6’ in the track ‘FLJ33706 Gene Structure’. The exons partially derived from re-sequenced data were highlighted in green. An ORF with two short coding exons located at exon 3 and exon 4 was identified to encode a 194-amino-acid-long peptide (track ‘Open Reading Frame (ORF)’). Newly inserted transposable elements, especially Alu sequences, contributed substantially to the formation of the first coding exon and six standard splicing junctions on the branch leading to human and chimpanzee, marked as ‘a,f’ in the track ‘FLJ33706 Gene Structure’. All repeat elements in this region were shown in track ‘RepeatMasker’, extracted from UCSC Genome Browser. Coding exons in tracks ‘Spliced Human EST’, ‘Human mRNA’ and ‘FLJ33706 Gene Structure’ were represented by higher vertical bars, while UTR regions and intronic regions were represented by lower vertical bars. Size scales were added in the figure to give benchmarks for gene sizes. Tracks with different size scales were separated by horizon lines. doi:10.1371/journal.pcbi.1000734.g001
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Hominoid-specific de novo protein-coding genes originating from long non-coding RNAs.

Hominoid-specific de novo protein-coding genes originating from long non-coding RNAs.

Our data supports that de novo origination rather than ORF expansion drove the origination of hominoid-specific ORFs. The ORF expansion model, which believes that a shorter ORF may predate the human-rhesus split, predicts that the longer the ORF in rhesus macaque relative to the ORF in human, the stronger the transcriptional correlation between them. The model also predicts that human de novo genes encoding multiple exons are more likely Figure 2. Strand-specific RNA–Seq in five rhesus tissues reveals clear transcript structure for de novo genes. (A) An example of de novo gene ENST00000315302 partially overlapped with a pre-existing gene ODZ3, transcribed by the other strand of the DNA. The ortholog of ENST00000315302 in rhesus macaque was aligned according to genome-wide multiple alignments in UCSC. The junction reads generated by strand- specific RNA-Seq assays are highlighted by black bold lines, with fragments of junction reads crossing splicing junctions connected by thinner lines. The mapped reads well supported the transcription of the target de novo gene on the reverse strand, as most reads appeared in the track for ‘reads transcribed from the minus-strand’. Regions for all four splicing junctions are highlighted in dotted boxes and expanded in (B), including three in ENST00000315302 transcribed from the minus strand and one from the other strand. All of these splicing junctions were well supported by the RNA- Seq reads mapped on the corresponding strand of the DNA. Vertical dotted lines in brown or blue highlight the exon boundaries in transcripts on the minus or plus strands, respectively. (C) Demo case for a discarded de novo gene in the manual curation process, in which the RNA-Seq data in rhesus macaque were not consistent with the putative splicing pattern predicted on the basis of human gene models. The common disabler is marked with a red star, and this was actually spliced out in rhesus macaque as indicated by the junction reads. Scale bar shown as benchmark for gene size. doi:10.1371/journal.pgen.1002942.g002
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Human disease-associated genetic variation impacts large intergenic non-coding RNA expression.

Human disease-associated genetic variation impacts large intergenic non-coding RNA expression.

Localization of lincRNA cis-eQTLs in regulatory regions We found that more than 70% of the lincRNA cis-eQTLs from both blood and non-blood tissues were located in intergenic regions with respect to protein-coding genes (Figure 2A). We also found high frequencies of lincRNA cis-eQTLs to be located around transcriptional start site (Figure 2B), suggesting that these cis-eQTLs may affect the expression of lincRNAs through similar gene regulatory mechanisms as those seen for protein-coding cis- eQTLs. Thus, in order to understand the mechanism of how lincRNA cis-eQTLs affect lincRNA expression, we intersected the location of top 112 lincRNA cis-eQTLs and their proxies (r 2 = 1) in blood with regulatory regions using the HaploReg database [26]. The results suggested that indeed most of the lincRNA cis-eQTLs (69%) were located in functionally important regulatory regions (Figure S8), which contained DNAse I regions, transcription factor binding regions, and histone marks of promoter and enhancer regions. Furthermore, these cis-eQTLs were found to be located more often within blood cell-specific enhancers (K562 and GM12878) (Figure 3A), suggesting that some of these cis-eQTLs regulate lincRNA expression in a tissue-specific manner through altering these enhancer sequences.
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The RNA helicases AtMTR4 and HEN2 target specific subsets of nuclear transcripts for degradation by the nuclear exosome in Arabidopsis thaliana.

The RNA helicases AtMTR4 and HEN2 target specific subsets of nuclear transcripts for degradation by the nuclear exosome in Arabidopsis thaliana.

In animals and fungi, a single MTR4 protein is present in nucleoplasm and nucleoli, and essential for both processing/ degradation of rRNA precursors and the elimination of all other nuclear exosome substrates [8–10,57]. However, both yeast and human MTR4 proteins are incorporated in more than one exosome activator/adapter complex. Yeast MTR4 is detected in TRAMP4 and TRAMP5 (for TRF4/5 AIR1/2 MTR4 Polyad- enylation), each of which comprises a RNA binding protein and a non-canonical poly(A) polymerase [58–61]. Although TRAMP4 and 5 have a similar composition and many redundant functions, TRAMP5 seems be more important for the polyadenylation of pre-rRNAs while TRAMP4 might be more important for the degradation of other non-coding RNAs and intergenic transcripts [62–64]. The functional specialization between nucleolar and nucleoplasmic exosome activator complexes is clearer in human. In nucleoli, hMTR4 is incorporated in a TRAMP-like complex which polyadenylates rRNA maturation by-products [9]. In the nucleoplasm, hMTR4 is associated with the NEXT (for Nuclear EXosome Targeting) complex, which targets PROMPTS (PRO- Moter uPstream TranScripts) for degradation by the exosome [9]. Hence, both yeast and animals possess nucleolar and nucleoplas- mic exosome activators, which share MTR4 as a central component. By contrast, an exosome activating system with two specialized RNA helicases has evolved early in the green lineage. Interestingly, both the nucleoplasmic fraction of human MTR4 and the Arabidopsis nucleoplasmic-specific RNA helicase HEN2 appear associated with similar RNA binding proteins to form NEXT and NEXT-like complexes, respectively, and with the cap- binding complex [9,21, this study]. These findings suggest a high degree of functional conservation between the nucleoplasmic fraction of human MTR4 and plant HEN2. By contrast, a TRAMP-like complex comprising a non-canonical poly(A) poly- merase remains to be identified in plants. Hence, the emerging picture is that only the core exosome machinery is conserved in all eukaryotes, while exosome-associated activities and activating complexes show intriguing diversity and complexity in fungi, insects, animals and plants.
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Evolution of the aging brain transcriptome and synaptic regulation.

Evolution of the aging brain transcriptome and synaptic regulation.

We have compared the protein-coding transcriptome of the aging cerebral cortex in mice, rhesus monkeys, and humans by utilizing species-specific genome-scale microarrays. As such, this study is not confounded by cross-species hybridization of RNA to microarrays, and provides a broad view of the evolution of the mammalian aging brain. Our results suggest that a relatively small subset of age-regulated gene expression changes are conserved from mouse to man. The most robustly age-upregulated of these conserved genes is apolipoprotein D, which has been shown to protect against oxidative stress and extend lifespan in Drosophila Figure 5. Global repression of genes associated with GABA-mediated inhibitory neurotransmission. Shown are age-related changes in the expression of genes that mediate major neurotransmitter systems in the cortex of humans, rhesus monkeys, and mice. a. Genes involved in specific neurotransmitters were identified based on membership in the corresponding GO groups. Age-related fold changes in genes with orthologs in all three species and represented on all three microarray platforms are shown for humans, rhesus monkeys, and mice. Gene identities are provided in Table S11. * q-value#0.01. b. Age-related fold changes for markers of inhibitory neuronal subpopulations. Statistical significance in a specific
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Comparative analysis of human protein-coding and noncoding RNAs between brain and 10 mixed cell lines by RNA-Seq.

Comparative analysis of human protein-coding and noncoding RNAs between brain and 10 mixed cell lines by RNA-Seq.

human brain tissues and a variety of cell lines. We found that under our selection criteria, the majority of (more than 60%) the expressed genes in both brain and cell lines generated only one isoform with relative higher level that can be detected, whereas a portion of the expressed genes could encoded more than five isoforms. In those expressed genes of brain and cell lines, a number of them could encode both protein-coding and noncoding RNAs through alternative splicing, implicating the intricacy of gene transcription and post-transcriptional RNA processing. We also found that although most of the expressed genes in human brain and cell lines are the same, but their expressions are significantly different at the isoform level, and only less than 30% of the isoforms are identical between brain and cell lines. Besides that, some expressed genes only generated protein-coding or noncoding transcripts in one sample but not in another. Our results reveal that the significant difference for gene expression profiles between brain and cell lines is not only relevant to the sequence compositions of their isoforms, but also associated with the protein-coding capacities of their isoforms. Furthermore, when taking the expression level of each isoform into consideration, the variations for gene expression will inevitably increase more dramatically. Accordingly, only based on the isoform level, can we accurately recognize the gene expression pattern and estimate the gene expression profiles in various biological conditions and different tissues, such a fine scale will definitely improve our ability to gain new important insights into the functionalities for each gene on the human genome.
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Cytokine Profile Associated with Human Chronic Schistosomiasis Mansoni

Cytokine Profile Associated with Human Chronic Schistosomiasis Mansoni

Responses of patients who remained untreated fol- lowing initial assessment. Even after an active search, 21 patients missed treatment that should be performed at the end of the study, and remained untreated after one year from their first ultrasonography examination. Ultrasonog- raphy was repeated on these individuals and 19 (90%) of them were found to have increased periportal thickness and 2 of them remained with similar measurements. Within this group, 12/19 (57%) exhibited more severe fibrosis compared to the previous exam. In 3 patients the fibrosis index had changed from degree 0 to degree I, and in 9 patients the fibrosis index had increased from degree I to degree II. Immunological evaluation was repeated in these patients and compared with the first evaluation. An in- crease in the levels of some cytokines was observed in SEA-stimulated PBMC supernatants. Levels of IFN-γ were evaluated in 18 patients and 2 patient presented a de- crease but the others did not show any significant change in the second versus first evaluations (Fig. 4A). TNF-α levels increased in 5 patients and decreased in 2 patients and remained at similar levels in 8 of the 15 patients tested (Fig. 4B). IL-5 levels increased in 9 patients, decreased in 1 patient and remained at similar levels in 8 of the 18 pa- tients tested (Fig. 5A), and IL-13 levels showed a major increased in 5 patients, a minor increase in 2 patients and decreased or remained at similar levels in 2 of the 9 pa- tients tested (Fig. 5B). The levels of IL-5 and IL-13 were significantly higher in the second evaluation (206 ± 434
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Arq. NeuroPsiquiatr.  vol.71 número10

Arq. NeuroPsiquiatr. vol.71 número10

is notable that they found a polymorphism in the 3_UTR of the TUBB1 gene, which was present in almost all patients but not in Brazilian normal controls. Because reverse-trans- criptase PCR analysis did not show any alteration in TUBB1 expression, it was then used as an intrafamilial marker. In ad- dition, this polymorphism reduced the interval to 1.5 Mb bet- ween the marker D20S430 and the TUBB1 gene. his region contains nine genes (a Z-DNA binding protein gene; a pros- tate androgen-induced RNA; an oncogene; and genes enco- ding a protein phosphatase, an aminopeptidase-like protein, a protein involved in imprinting, a Drosophila-like protein, and two proteins involved in intracellular traicking) and seven hypothetical or predicted genes. Mutation screening in these candidates genes led to the identiication of a CrT substitution in exon 2 of the VAPB gene. his proline is con- served in several species, such as H. sapiens, M. musculus, R. norvegicus, A. californica, D. melanogaster, and S. cerevi- sae. his mutation was present in all afected members in their family 1 but not in unafected relatives or in 400 chro- mosomes of unrelated normal controls. Subsequently, they found the same mutation in 22 patients from 6 additional large Brazilian kindreds with inter- and intrafamilial clinical heterogeneity. Although it was not possible to link all these families, the haplotype analysis with nine polymorphic mar- kers lanking the VAPB gene suggests a common ancestor and, therefore, a founder efect 1
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Rev. Soc. Bras. Med. Trop.  vol.49 número5

Rev. Soc. Bras. Med. Trop. vol.49 número5

There were no signiicant indings in her prenatal history. The patient was born via cesarean section due to cephalopelvic disproportion and was breastfed until the age of 3 years. The patient’s mother was 32 years and had a known HTLV-1 infection, which was diagnosed at 11 years. The infection manifested as HTLV-1-associated myelopathy (HAM) with a progressive course. The patient’s mother was born vaginally and was breastfed until the age of 4 years. The mother also stated that the patient’s grandmother was an asymptomatic carrier

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Cardiovascular disease associated with human immunodeficiency virus : a review

Cardiovascular disease associated with human immunodeficiency virus : a review

A retrospective analysis of causes of death in 13 cohort studies of HIV type 1 (HIV-1)-infected patients who initiated antiretroviral therapy (ART) in Europe and North America from 1996 through 2006 showed lower mortality from AIDS- related causes and higher mortality from causes associated with aging, such as non-AIDS malignancies and cardiovascu- lar disease (CVD). The latter accounted for 7.9% of deaths, of which 40% were from myocardial infarction (MI)/ischemic heart disease (IHD), which suggests that the process of aging will become a dominant factor in HIV-1 mortality in the next decade. 2
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Mediated Immortalization of Human Bone Marrow Stromal Cells

Mediated Immortalization of Human Bone Marrow Stromal Cells

Cell immortalization refers to the characteristic of continuous proliferation of the cells (Satija et al. 2007). In several studies, exogenous virus, or oncogene has been introduced to target the cells to construct the immortalized cells (Kelekar and Cole 1987; Arimura et al. 2007; Wu et al. 2007), in which the integration of target gene was random and expression of target gene might have interfered with the intracellular physiological processes, which could result in unexpected changes such as loss of differentiation characteristic and lack of control of check point. The cells treated with virus, or oncogene belong to transformed cells but not the normal cells, and thus they are different partially, or completely from the normal cells in the transformation features such as changes in cell morphology, karyotype and tumorigenicity, as well as loss of suspended growth and contact inhibition (Gipson et al. 2007). The hTERT gene is an immortalization gene. If the exogenous hTERT could be transfected into the target cells and expressed stably, the reverse transcription activity of telomerase would increase to promote the reverse transcription of telomerase RNA. In addition, hTERT can also protect, or stabilize the telomerase RNA to prolong the half life of telomerase RNA (Petersen and Niklason 2007). The hTERT gene is an immortalization gene and exogenous hTERT can activate the activity of telomerase in target cells and maintain the length of telomere. Then, cells can pass the senescence phase (M1 phase) and crisis phase (M2 phase), leading to immortalization (Petersen and Niklason. 2007). Bodnar et al (1998) found that transient expression of the hTERT in normal diploid cells could activate the telomerase activity and prolong the cell survival. The hTERT has been successfully introduced to human periodontal
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Looking at tricellulin expression in the brain

Looking at tricellulin expression in the brain

TRIC assembly at tTJ in cochlear and vestibular epithelial cells appears to play a key role in hearing, as mutations in the TRIC gene were associated with deafness (Riazuddin et al., 2006). It is known that TRIC protein is present at tricellular contacts of vestibular and cochlear epithelia and mutations of TRIC-a, the longest human isoform, have been reported to result in a human hereditary disease, nonsyndromic deafness (DFNB49). A common feature of the four DFNB49 TRIC alleles is that they encode predicted truncated proteins that lack the ability to bind to the scaffolding protein ZO-1, because of the loss of the conserved C-terminal occludin-ELL domain, and as previously described, this can interfere with the localization to TJs. In contrast, Raleigh, et al., (2010) suggested that TRIC may interact with ZO-1 at another site, because their studies show that C-terminus of TRIC was not able to bind ZO-1 GK domain. Alternatively, minor differences between the TRIC tails constructs used in both studies may explain the disparate observations. In fact, it has been speculated the relation between mutations in TJ gene and deafness. Mutations in claudin 14 gene are associated with different hearing thresholds, including profound and congenital deafness, but the role of this protein in hearing process is still unknown (Bashir et al., 2010; Ben-yosef et al., 2003). Yet, the only obvious phenotype of mutant alleles of Tric is deafness. It is possible that some other molecule compensates for the absence of wild-type TRIC in other epithelial cell types but not in the inner ear.
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Cognitive demands of lower paleolithic toolmaking.

Cognitive demands of lower paleolithic toolmaking.

("chunking" [30]) suggest greater working memory demands during learning vs. expert perfor- mance. To address this, we employed a longitudinal design, training subjects for two years in a variety of archaeologically attested Paleolithic toolmaking methods and conducting fMRI ex- periments at the start (T1), mid-point (T2), and end (T3) of training. This demanding training program limited sample size but enabled investigation of the acquisition of a real-world, evolu- tionarily-relevant skill in a manner not previously achieved in either archaeology or neurosci- ence. We evaluated behavioral and brain responses to stimuli representing simple flake production (cf. “Oldowan”, “Mode 1”, “Mode C” [31], hereafter "Oldowan") and refined biface shaping (cf. “Later Acheulean handaxe”, “Mode 2”, “Mode E2” [31], hereafter "Acheulean"). We predicted an interaction between Task (Prediction vs. Strategy), Technology (Oldowan vs. Acheulean), and Time (T 1, 2, 3) such that prefrontal response would be greater for the Strate- gy task, especially with respect to the more complex Acheulean technology and at earlier stages of skill acquisition. Our training program also allowed us to study tools produced by our re- search subjects outside the scanner [32]. We expected that individual performance on our MRI tasks would be predictive of actual success with stone toolmaking.
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Characterization of the Drosophila group ortholog to the amino-terminus of the alpha-thalassemia and mental retardation X-Linked (ATRX) vertebrate protein.

Characterization of the Drosophila group ortholog to the amino-terminus of the alpha-thalassemia and mental retardation X-Linked (ATRX) vertebrate protein.

Figure 1. The ADD domain of the hATRX protein is conserved in the dAdd1 proteins of Drosophila. A. ADD domain prediction in the protein sequence alignment of hATRX and dAdd1 proteins. Conserved cysteines are shown as yellow letters within a cyan box. The amino acids involved in H3K9me3 and H3K4me0 recognition are marked by green and red boxes respectively. The GATA-like C2-C2 zinc finger and the C4-C4 imperfect PHD are marked by green and red boxes respectively. B. Ribbon representation of ADD domain of hATRX on red (left) and dAdd on green (center) CPH models-3.0 server was used to create the model of the ADD domain of dAdd1. Structural superposition of ADD domains of hATRX and dAdd1 (right). C. Domain organization of dAdd1 (a-c) isoforms. All of them have an N-terminal ADD domain. A C-terminal MADF domain is present in two (dAdd1-b, and dAdd1-c isoforms) copies. D. Maximum Likelihood Phylogenetic Analysis of the ADD domain and the corresponding Protein Domain Architecture information of the containing proteins as computed by PhyML [16] and ScanProsite [19], respectively. The numbers shown represent bootstrap values. Note that the ADD harboring protein underwent a gene fission event during the evolution of insects. Also note that the homologous proteins within the Drosophila genus have acquired a tandem MADF domain during its divergence from other insects. This domain is likely to be functional given its conservation within the genus. For the parameters used, refer to Material and Methods.
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Molecular biology of the kallikrein-kinin system: from structure to function

Molecular biology of the kallikrein-kinin system: from structure to function

ting mechanisms (1). Pharmacological stud- ies have demonstrated that kinins promote their biological activities through the activa- tion of at least two different receptor sub- types, denominated B1 and B2. Stimulation of the B2 receptor results in intense vasodi- lation, increased blood flow and hypoten- sion (1). In the central nervous system, how- ever, bradykinin (BK) promotes systemic vasoconstriction, increased peripheral resis- tance and hypertensive responses also via stimulation of B2 receptors (2). Other ef- fects mediated by B2 receptors include con- traction of the bronchopulmonary tree, in- creased sperm motility, release of cytokines, prostacyclin, and nitric oxide, as well as stimulation of cell proliferation (1). BK, kal- lidin and the other intact kinins can exert their biological function by binding with high affinity to the B2 receptors whereas the products of the action of the arginine carbox- ypeptidase (kininase I-activity) on kinins, the C-terminal-arginine truncated kinins, are preferential agonists for the B1 receptor (3- 5). The B1 receptor is believed to mediate several of the inflammatory responses to kinins (1) and, under pathological condi- tions, contractile effects on visceral smooth muscle (6). The B2 receptors are constitu- tively expressed and widely distributed throughout mammalian tissues. In contrast, the B1 subtype is very weakly expressed under normal conditions but can be induced in vivo and in vitro by endotoxin, cytokines and growth factors, indicating that these re- ceptors may be important in inflammation and trauma (1). Lately, due to the recent advances in genetic and molecular biology techniques, the role of the KKS in several physiological processes can be analyzed in more detail using different transgenic ani- mal models.
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Principal component analysis of the cytokine and chemokine response to human traumatic brain injury.

Principal component analysis of the cytokine and chemokine response to human traumatic brain injury.

Statistical analysis was performed using multivariate techniques, specifically principal component analysis (PCA), followed by partial least squares discriminant analysis (PLS – DA). SIMCA – P+ version 12 (Umetrics, Umea, Sweden) was used to identify principal components which accounted for the majority of the variation within the dataset. PCA is an unsupervised method and a data reduction technique that allows the major sources of variation in a multi-dimensional dataset to be analysed without introducing inherent bias. PLS – DA is a regression extension of the principal component analysis that uses class information to maximize the separation between various groups of observations. To estimate the number of PCA and PLS-DA components, cross-validation was used [21]. Data for each cytokine was mean centred and variance scaled to unit variance. SIMCA-P+ uses NIPALS (non- linear iterative partial least squares) algorithm to calculate the first few principal components and inherently compensates for missing data values. This has been suggested as a more accurate, though computationally more complex method for deriving eigenvalues [24]. Cross validation was carried out by dividing the data into seven parts and comparing models with each of the seven parts left in or out in turn. Predicted Residual Sum of Squares are calculated for the whole dataset and scaled to provide the Q2 statistic.
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Gene expression analysis in human breast cancer associated blood vessels.

Gene expression analysis in human breast cancer associated blood vessels.

Frozen sections (8 m m thickness) were fixed in acetone for 5 min (220uC), washed in PBS, blocked with 5% BSA/PBS for 30 min and incubated with primary antibodies (LIFR: 1/50, Santa Cruz sc-659; GPR164: 1/400, Abcam ab65759, CD31: 1/100, BD Pharmingen 550389) overnight at 4 uC. Sections were washed in PBS before adding the appropriate fluorescent secondary antibodies for 1 hr at room temperature and mounted with ProLong GoldH anti-fade reagent with DAPI (Invitrogen P- 36931). Sections were imaged using a LSM 510 inverted confocal laser-scanning microscope (Carl Zeiss Ltd., UK). For each channel, the detector gain and amplifier offset were set to display the full range of signal intensities within and between samples and then adjusted to exclude background. These settings were kept the same when imaging all the patients’ samples. Consecutive sections from each patient were also stained with appropriate IgG control antibodies and imaged using the same settings. Staining was quantified in the CD31-positive blood vessels using ImageJ software. Blood vessels were identified by their CD31 positivity and the corresponding GPR164 or LIFR fluorescence intensity per pixel was measured. ImageJ software was used to evaluate the mean relative intensity of fluorescence for these markers in blood vessels within the sections. In order to normalise blood vessel- specific immunostaining for GPR164 and LIFR between samples, it was necessary to correct for differences in non-specific staining. This was done by analysing the mean fluorescence intensity of IgG non-specific staining in the CD31-positive blood vessels and then Figure 3. Affymetrix data from LCM blood vessels. (A) Hierarchal clustering of laser captured blood vessels from 4 normal and 5 IDC samples with percentage present call rate. (B) Heat map that shows the trend in expression of 73 probe-sets, 70 genes across the six samples. The blue indicates under-expression while the red indicates over-expression with gene name and accession number given.
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Behavioral responses associated with a human-mediated predator shelter.

Behavioral responses associated with a human-mediated predator shelter.

Human activities in protected areas can affect wildlife populations in a similar manner to predation risk, causing increases in movement and vigilance, shifts in habitat use and changes in group size. Nevertheless, recent evidence indicates that in certain situations ungulate species may actually utilize areas associated with higher levels of human presence as a potential refuge from disturbance-sensitive predators. We now use four-years of behavioral activity budget data collected from pronghorn (Antilocapra americana) and elk (Cervus elephus) in Grand Teton National Park, USA to test whether predictable patterns of human presence can provide a shelter from predatory risk. Daily behavioral scans were conducted along two parallel sections of road that differed in traffic volume - with the main Teton Park Road experiencing vehicle use that was approximately thirty-fold greater than the River Road. At the busier Teton Park Road, both species of ungulate engaged in higher levels of feeding (27% increase in the proportion of pronghorn feeding and 21% increase for elk), lower levels of alert behavior (18% decrease for pronghorn and 9% decrease for elk) and formed smaller groups. These responses are commonly associated with reduced predatory threat. Pronghorn also exhibited a 30% increase in the proportion of individuals moving at the River Road as would be expected under greater exposure to predation risk. Our findings concur with the ‘predator shelter hypothesis’, suggesting that ungulates in GTNP use human presence as a potential refuge from predation risk, adjusting their behavior accordingly. Human activity has the potential to alter predator-prey interactions and drive trophic- mediated effects that could ultimately impact ecosystem function and biodiversity.
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Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity.

Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity.

Accumulation of mutant SOD1 proteins into visible foci, although consistent with their in vitro aggregation propensity, does not necessarily indicate the formation of aggregates. We used dynamic imaging and FRAP analysis to establish the aggregation state of SOD1 proteins in live animals. As shown in Figure 2A, the diffusion of WT SOD1-YFP fusion protein in body wall muscle cells (light blue) was indistinguishable from that of YFP alone (purple), with nearly complete recovery within the dead-time of measurement post bleaching. In contrast, the fluorescent foci of all three mutant proteins exhibited reduced recovery indicative of immobile aggregate species (Figure 2A,B). G85R and G93A proteins had 35 and 50% recovery over 275 seconds, respectively, higher than that observed for foci of well-characterized aggrega- tion-prone polyQ40 (30%), which contain only an immobile protein [34]. The recovery of fluorescence in 127X foci continued beyond 100 sec and reached nearly 60% over the course of the experiment, which suggests either partially mobile species, or the presence of multiple populations of protein.
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Rev. Bras. Hematol. Hemoter.  vol.38 número1

Rev. Bras. Hematol. Hemoter. vol.38 número1

An additional unusual aspect of this case is the rare over- lap of HTLV-1-related diseases: HAM/TSP and a hematological disorder. ATL and HAM/TSP seem to differ in their route of transmission (ATL being mainly via breast-feeding, and HAM/TSP via blood transfusion), pathogenesis and immuno- logical response. After infection, both cellular and humoral immune responses are formed against HTLV. The humoral reaction contributes as delayed protection by producing anti- bodies against viral proteins, including Tax. However, recently, Tax-antibodies have been associated with the development of HAM/TSP, suggesting an autoimmune component to the disease. This antibody could also be associated with AIMF. Fur- thermore, HAM/TSP apparently relates to patients with high proviral loads, which is supposedly determined by host fac- tors such as polymorphisms in the major histocompatibility complex class I (MHC-I) molecules and its influence on antigen presentation to CD8 + T-cells.
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