We extracted the coding sequences mapping to each gene by using E

We extracted the coding sequences mapping to each gene by using E. grandis gene annotation file. We used a minimum coverage of 20 reads, a maximum coverage of 8000, minimum phred quality of 20 and a minimum allele count of 4 for identifying the variants. The maximum coverage inhibitor Tipifarnib was based on the observed maximum SNP coverage of 7961 Inhibitors,Modulators,Libraries reads with a minimum base quality of 20. The identity of the variants was fur ther confirmed by visual inspection of the tracks in inte grative genomics viewer. We uploaded the BAM files, the SNP position files and E. grandis gene an notation files into IGV and visually inspected the variants from different genes to confirm the annotations. The identified nonsynonymous and synonymous SNPs were normalised by non synonymous and synonymous lengths calculated using the PoPoolation package.

The average nonsynonymous length of each codon was cal Inhibitors,Modulators,Libraries culated using transversion penalty of 6. The synonymous length was calculated as 3 nonsynonymous length. Inhibitors,Modulators,Libraries The Ka Ks ratios were estimated following Novaes et al. by adding a unit to both nonsynonymous and synonym ous sites. To identify the gene categories enriched among the positively Inhibitors,Modulators,Libraries and negatively selected genes we conducted the GO tests by comparing the gene categories enriched among positively and negatively selected genes separ ately. To identify the gene categories enriched among the positively selected genes, all the genes with Ka Ks ratios more than 1. 5 were compared with the rest of the genes. Similarly to identify the genes enriched among the nega tively selected genes, all the genes with Ka Ks ratios less than 0.

20 were compared with the rest of the genes. GOMiner package was used for GO analysis of the selected genes. Drosophila melanogaster development requires the pre cise coordination of multiple distinct gene regulatory mechanisms and processes within, between, and among different cell types. One such process, RNA turnover, ensures that free nucleotides are salvageable for use in Inhibitors,Modulators,Libraries transcription, signalling, transport, and protein transla tion. RNA turnover is especially important during cellu larization, when all maternally deposited RNAs are degraded. Yet, surprisingly, the full set of ribonu cleases and RNA binding proteins that contrib ute to developmentally regulated RNA turnover��both maternal and zygotic RNAs��remain unknown.

Dis3��a 3 to 5 not exoRNase and endoRNase��has vital, conserved roles in RNA turnover and surveillance in eukaryotic cells. A homolog of the prokaryotic RNase II and RNase R, Dis3 has been proposed to be the major ribonucleolytic activity in the RNA processing exosome, a protein complex consisting of the nuclear 3 to 5 exoribonuclease Rrp6, RNase PH subunits Rrp41 Ski6, Rrp42, Rrp43, Rrp45, Rrp46 and Mtr3, and S1 domain subunits Rrp4, Rrp40 and Csl4.

In addition, Ser37 was pre dicted by the motif prediction program

In addition, Ser37 was pre dicted by the motif prediction program to scientific assay be phosphorylated by Casein kinase II. However, this possi bility needs to be experimentally evaluated in the context of apoptosis and will provide detailed insight into CTMP regulation. CTMP was detected in the membrane and cytosol fraction of LN229 cells. Furthermore, two molecular species corresponding to CTMP were observed in different cell lines, suggesting post translational modifications. In addition, CTMP associated with intracellular structures similar to membrane ruffles. Recently, a nuclear pool of CTMP was detected in human pancreatic duct epithelial cells. Consistent with recent reports, a mito chondrial pool of CTMP from HEK 293 cells dependent on its MTS was detected in our experiments.

Furthermore, this mitochondrial CTMP localization was inhibited by phosphorylation. Therefore, CTMP may have distinct roles in various subcellular com partments. Mitochondrial localization is mediated by the MTS. In most cases, the MTS is present as a cleavable sequence at the N terminus, also Inhibitors,Modulators,Libraries called a pre sequence. Bioinfor matic analysis of the CTMP sequence indicated that a potential MTS exists in CTMP at the N terminus of pro tein. This predicted N terminal MTS appears to be func tional since an N terminal 31 amino acid deletion mutant of CTMP did not localize to the mitochondria. N terminal MTS of mitochondrial precursors are in most cases cleaved by the mitochondrial processing peptidase as soon as Inhibitors,Modulators,Libraries the cleavage sites reach the mitochondrial matrix.

Mutational stud ies show the R 2 or R 3 motif are important but not suffi cient to direct cleavage by MPP. Site directed mutagenesis of the 2 or Inhibitors,Modulators,Libraries 3 arginine in different precursor molecules completely or partially inhibits processing. Further studies are needed to interrogate Inhibitors,Modulators,Libraries if the R 2 motif of CTMP is important in MTS mediated mito chondria localization. The molecular pathways that mediate apoptosis are tightly regulated by a series of positive and negative sig nals, the balance of which determines whether or not cells commit suicide. Recent evidence indicates that the coordinated interaction between Hsps and the compo nents of apoptosis machinery may determine cellular sus ceptibility to damaging stresses. Indeed, CTMP associate specifically Hsp70, but not Hsp90, in HeLa cells.

Furthermore, complex formation of Hsp70 and Apaf 1 was decreased in CTMP infected cell compared to controls, indicating why CTMP overexpression sensitized the cell to apoptosis induced by staurosporine. Indeed, Miyawaki and col leagues recently reported that upregulation Inhibitors,Modulators,Libraries of CTMP in hippocampal neurons is required for ischemia http://www.selleckchem.com/products/GDC-0449.html induced neuronal death. Based on previous studies, anti GFP, anti PARP, anti Flag, HRP conjugated anti mouse IgG, HRP conjugated anti rabbit IgG, and HRP conjugated anti sheep IgG antibody.

Plants have developed various mechanisms to defend themselves aga

Plants have developed various mechanisms to defend themselves against herbivorous insects. In addition to nonspecific, constitutively expressed physical and chemical barriers, plants employ specific induced defenses in re sponse to insect feeding or even egg laying. In contrast to feeding, insect egg laying causes min imal damage to plants, dependent on the egg Carfilzomib laying be havior of herbivorous insects, which can be quite distinct in different species. Direct defenses against insect eggs have been reported for crop and herbaceous species including the production of ovicidal substances, growth of neoplasms, development of necrotic zones. Indirect defense against insect egg laying includes induced changes of plant volatile emissions or modifications of the plant surface Inhibitors,Modulators,Libraries chemis try attracting or arresting egg parasitoids, which in turn kill the eggs of the herbivores.

The Inhibitors,Modulators,Libraries first study demonstrating indirect defense against insect eggs was a study of the field elm, where eggs of the elm Inhibitors,Modulators,Libraries leaf beetle induced volatiles which attract the egg parasitoid Oomyzus gallerucae, a tiny eulophid wasp specialized on elm leaf beetle eggs. Elm leaf Inhibitors,Modulators,Libraries beetles often feed and lay eggs on the same plant and are known to remove the leaf epidermis prior to egg laying by scratching the leaf surface with their mouthparts. Ex perimental simulation of this egg laying sequence by transferring eggs or oviduct secretion on scratched elm leaves or treatment with jasmonic acid or methyl jasmonate also elicited indirect defense responses in field elms.

A recent study further showed that terpenoids present in the odor of egg induced elm leaves are rele vant for attraction of the egg parasitoids. Induction of attractive plant volatiles by insect egg laying has been shown in one other tree species and two herbaceous crops. The natural range of the European field elm Ulmus minor extends Inhibitors,Modulators,Libraries predominantly within South ern Europe. However, through cultivation it occurs throughout the temperate world. Elms are greatly valued for their timber qualities and prior to the Dutch elm dis ease outbreaks, elms were also frequently planted within urban areas because of their environmental tolerance. Many insects including moths, gall mites, and beetles feed on field elms. The elm leaf beetle X. luteola can defoliate entire trees and is recognized as a major urban and forest pest in the USA and Australia. The recently published EST sequences for U. americana selleckchem Imatinib Mesylate is to our knowledge, the only other gene expression study of any Ulmus species, where 535 ESTs were identified after trees were exposed to the fungal pathogen Ophios toma novo ulmi, which is the causative agent of Dutch elm disease. Knowledge on how plants are able to respond at the molecular level towards egg laying is scarce.

5 fold relative to the DMSO control The most efficient com pound

5 fold relative to the DMSO control. The most efficient com pounds IDX 12899, GW 678248 and VRX 480773 selleck chem inhibitor showed strong b Gal activity enhancement at 250 nM, while 1 uM of ETV or EFV was required to achieve the maximal effect. At high NNRTI concentrations microscopically detectable impairment of cell growth, accompanied by a decrease in b Gal activity and high signal variability between replicates indicative of cyto toxic effects was observed, and concentrations above 2. 5 uM NNRTI were therefore excluded from the analysis shown here. this Inhibitors,Modulators,Libraries effect was most pronounced for TMC 120, ETV and VRX 480773. The cytotoxicity observed for TMC 120 under the conditions used, which was con firmed by CC50 determination using a T cell line, likely presents an Inhibitors,Modulators,Libraries explanation for Inhibitors,Modulators,Libraries a discrepancy between our findings and those of Figueiredo et al.

who had reported a stimulation of Gag processing upon shorter incubation of cells with 5 uM TMC 120. Under our experimental conditions we could Inhibitors,Modulators,Libraries not measure repro ducible b Gal activities at this concentration due to cell death. we can also not exclude that cytotoxicity might have obscured stimulatory effects of TMC 120 at lower concentrations. The ranking in the efficacy of compounds was confirmed by immunoblot analysis of lysates from cells incubated with 0. 5 uM of the respective inhibitors, which showed clear differences between the Inhibitors,Modulators,Libraries compounds with respect to the enhancement of Gag pro cessing directly paralleling the results obtained in the alpha complementation assay.

Selective PR dependent killing of HIV expressing Gemcitabine buy T cells by NNRTIs The described drug induced PR activation might be exploited to selectively kill HIV infected cells. In order to test this hypothesis, we established the persistently infected T cell lines MT4 IIIB and MT4 LTR EGFP IIIB, where the expression of HIV encoded proteins in 99% of cells could be detected by intracellular p24 staining. In MT4 LTR EGFP IIIB cells, HIV expres sion could additionally be detected through long terminal repeat driven expression of the gfp marker gene. As a control we used uninfected MT 4 cells or MT4 CMV EGFP cells, constitutively expressing EGFP from a CMV promoter, respectively. The use of persistently infected cells enabled us to study the effects of NNRTIs on virus producing cells regardless of their effect on reverse transcription, since the proportion of virus pro ducing cells in this system does not depend on infection of new host cells. Immunoblot analysis of cell lysates after treatment with two of the more potent NNRTIs, VRX 480773 and GW 678248, confirmed that NNRTI mediated enhancement of Gag processing also occurred in virus producing cells, as apparent from the decreased ratio of Gag to intermediate and fully mature processing products.

Pro IL 1B is the sub strate

Pro IL 1B is the sub strate Ponatinib buy of the cysteine protease caspase 1, which mediates the cleavage of pro IL 1B and release of the mature, bio logically active cytokine form of IL 1B. Caspase 1 itself is present as an inactive proform in the cytoplasm, and is activated by proteolytic self processing. The induction of IL 1B secretion requires enhanced pro IL 1B synthesis through transcriptional mechanisms via NF ��B, followed by a second stimulus that leads to the activation of caspase 1, processing of pro IL 1B and release of mature IL 1B. The NLR NALP3 interacts with the adapter protein ASC to form the inflammasome that has been identified as cas pase 1 Inhibitors,Modulators,Libraries activator, and thus controls the second required step of IL 1B cytokine activation.

In the present work, we examined the signaling molecules that contribute to IL 1B activation in microglia in response to PrP106 126 stimulation. Inhibitors,Modulators,Libraries Our data indicate that the NLR protein NALP3 and the inflammasome adaptor ASC are involved in PrP106 126 induced caspase 1 and IL 1B acti vation. The siRNA mediated disruption of either NALP3 or ASC significantly attenuated but did not completely abro gated IL 1B production, as Inhibitors,Modulators,Libraries residual IL 1B was still detected. This may be due to the incomplete silencing of NALP3 or ASC with siRNA mediated disruption, or to the exist ence of alternative pathways for IL 1B activation. Indeed, recent reports have shown that inflammasome and caspase 1 independent mechanisms may also be involved in the activation of IL 1B in microglia.

A recent study showed that AB, an endogenous peptide that forms insoluble fibrils in the brains of patients with Alzheimers disease, activates the NALP3 inflam masome. Activation Inhibitors,Modulators,Libraries of the NLRP3 inflammasome Inhibitors,Modulators,Libraries by islet amyloid polypeptide has been also reported in type 2 diabetes. In the present study we found that the neurotoxic prion protein fragment PrP106 126, which forms amyloid fibrils with high B sheet content, also activates the NALP3 inflammasome. This supports a key role for the NALP3 inflammasome as a general sensor for the recognition of peptide or protein aggregates that are involved in the pathogenesis of diseases such as AD, prion diseases, and systemic amyloidosis. However, it is not clear whether inflammasome activation has a benefi cial or deleterious effect on the progression of amyloid associated diseases. Activation of NF ��B is known to be involved in PrP106 126 induced microglial activation. Our experiments indicate that inhibition of NF ��B activation abrogates PrP106 126 induced NALP3 mRNA upregula selleck inhibitor tion. This confirms that NF ��B activation acts upstream of NALP3, which is consistent with the well described role of NF ��B as the main regulator of IL 1B precursor synthesis.

Concurred with a recently published article with significantly en

Concurred with a recently published article with significantly enhanced angiogenesis and number of EPCs in the scientific assay ischemic zone in a rat CLI model after com bination therapy, remarkably elevation of the circulat ing level of EPCs was found in our patients after similar treatment for 90 days. Second, studies have previously re ported that proliferation of neo intimal growth of vascular smooth Inhibitors,Modulators,Libraries muscle cells plays a key role in the progression of restenosis and PAD as well as restenosis after PAD intervention. Additionally, as described in many studies clopidogrel and cilostazol harbor anti platelet and anti thrombotic effects while cilostazol can inhibit smooth muscle cell proliferation. Ac cording to the results of these studies, we believe that such effects may also contribute to the delight ful outcome of among our patients.

Third, as revealed by our results, clopidogrel and cilostazol combination therapy elicit potent anti inflammatory Inhibitors,Modulators,Libraries effect which is helpful in limiting the exacerbation of ulcers and aug menting would healing. The proposed Inhibitors,Modulators,Libraries mechanisms Inhibitors,Modulators,Libraries of clopidogrel and cilosta zol combination therapy in improving clinical outcome of CLI patients have been summarized in Figure 5 and described as the followings based on the findings of the current study and the previous reportsPlatelet activation in setting of CLI stimulated the acti vation and migration of peripheral leukocytes. Both activated macrophages and T cells then produced the galactin 3 which, in turn, promoted the focal adhesion turnover, cell migration, and RhoA activation.

Additionally, Lp PLA2 enhanced the generation of inflammatory cytokines and up regulated the inflammatory process. Finally, galactin 3, Lp PLA2 and RhoAROCK synergistically promoted the inflammation and ultimately Inhibitors,Modulators,Libraries worsened the wound ulcerations and pain ful sensation. On the other hand, combine ther apy with clopidogrel and cilostazol enhanced angiogenesis neovascularization which, in tern, improve blood flow in the ischemia zone, and finally, improved the wound healing. Study limitations This study has limitations. www.selleckchem.com/products/AG-014699.html First, the sample size of the present study was relatively small. However, the prelimin ary results clopidogrel and cilostazol combination therapy in CLI patients who are not amendable by surgical or endovascular methods are promising. Second, the 90 day study period in this initial trial was relatively short. The clinical benefits or drawbacks after long term combination therapy are not known. Third, in addition to clopidogrel and cilostazol combination therapy, patients were also sub jected to statin and ACIARB treatment during the study period and thus the effects or interaction of these drugs could hardly be validated.

In contrast, rapamycin

In contrast, rapamycin kinase inhibitor Bosutinib treated mice showed a focal loss of proteoglycan staining without severe articular cartilage loss at 8 weeks and lesions with a loss of proteoglycan staining slightly increased 12 weeks after surgery. however, hyaline cartilage was Inhibitors,Modulators,Libraries preserved. The extent of OA was evaluated by scoring specific parameters of OA, and is presented as summed scores. Using the summed OA score, DMSO treated mice developed OA in a time dependent manner and had a significantly higher score than the rapamycin treated mice at 8 and 12 weeks following DMM surgery. The summed OA score in the rapamycin treated Inhibitors,Modulators,Libraries mice at 12 weeks was increased compared to the score at 8 weeks. These results suggested that the intra articular injection of rapamycin did not completely prevent but delayed articular cartilage degradation in the presence of meniscus injury after DMM surgery.

The local intra articular injection of rapamycin decreased p mTOR and increased LC3 expression To determine whether the local intra articular injection of rapamycin modulates mTOR and autophagy, the effects that rapamycin had on phospho mTOR and LC3 expressions were examined. The expression of p mTOR was increased in DMSO treated mice Inhibitors,Modulators,Libraries at 8 and 12 weeks post DMM surgery compared to DMSO treated Inhibitors,Modulators,Libraries mice undergoing the sham knee operation. Rapamycin treatment suppressed p mTOR expression in these mice compared to those treated with DMSO at both the 8 and 12 week time points post DMM injury. The expression of p mTOR in the rapamycin treated mice was significantly increased at 12 weeks compared to 8 weeks after DMM injury.

In contrast, LC3 positive cells were higher in the articular cartilage maintaining proteoglycan staining but lower in the degenerated articular cartilage of the DMSO treated mice after DMM surgery. An increased in LC3 positive cells was observed in the rapamycin treated mice compared to those treated with DMSO at 8 and 12 weeks post DMM surgery. The number of LC3 positive Inhibitors,Modulators,Libraries cells in the rapamycin treated mice decreased significantly at 12 weeks compared to 8 weeks post DMM injury. Figure 2 The effect of rapamycin on p mTOR and LC3 expressions. Representative images of immunostaining for p mTOR and LC3. Scale bar 20 um. Quantification of p mTOR positive cell was calculated. Rapamycin treatment suppressed p mTOR expression in the rapamycin treated mice compared to those treated with DMSO Volasertib cost at both the 8 and 12 week time points. Quantification of LC3 positive cells was calculated.

The mecha nism of tumor resistance to the monoclonal antibodies b

The mecha nism of tumor resistance to the monoclonal antibodies bevacizumab and cetuximab is not well understood and warrants further investigation. It is also possible that vandetanib MEK162 treatment may induce hemodynamic changes, such as normalization remode ling of the tumor vasculature as hypothesized by Jain, that would not necessarily be detected by estimating changes in Ktrans and iAUC60. More complex DCE MRI approaches such as the St Lawrence and Lee model, which is able to derive independent measurement of blood flow, blood volume and permeability surface area, may be more appropriate for detecting complex changes in tumor vascularity and hemodynamics. Normalization of the tumor vasculature might also be expected to improve tumor oxygenation and blood flow.

In this regard, the results from the exploratory assessment of T2 using intrinsic susceptibility MRI merit discussion. Changes in T2 can be used to monitor changes in deox yhemoglobin and an increase in T2 could Inhibitors,Modulators,Libraries result from improved tumor oxygenation and blood flow. However, T2 is influenced by other fac tors and is therefore a difficult parameter to interpret on its own. In the absence of detectable effects on tumor hemodynamics as measured by DCE MRI, an increase in T2 could be attributed to an increase in tumor cell death. As such, the significant increase in T2 at vandetanib 300 mg compared with 100 mg in the present study may reflect increased tumor necrosis at the higher dose. Further Inhibitors,Modulators,Libraries correlative work is needed to under stand the biological basis of changes in T2 in the clinical setting.

Population pharmacokinetic pharmacodynamic analyses showed no correlation between vandetanib exposure and any of the pharmacodynamic parameters analyzed. Given the long half life of vandetanib, it may take up to 4 weeks for vandetanib to reach steady state, in the present study, steady state was attained Inhibitors,Modulators,Libraries from day 15 at the earliest, but was mostly from day 22 onwards. It is not fully under stood how tumor growth adaptation during this pro longed period of drug accumulation may affect pharmacodynamic variables. Conclusion In the present study, DCE MRI assessments of iAUC60 and Ktrans provided no evidence that vandetanib modulated gadolinium uptake within the tumor vasculature of patients Inhibitors,Modulators,Libraries with advanced colorectal cancer and liver metas tases.

As discussed, these findings from a small open label study of only 24 patients should be interpreted with cau tion, particularly since vandetanib has previously demon strated evidence of antitumor activity in phase II studies in advanced NSCLC and medullary Inhibitors,Modulators,Libraries thyroid cancer that sellckchem is consistent with inhibition of VEGFR activity. Vandetanib is one of a number of VEGF signaling inhibitors in clinical development and each has a different pharmacological profile.

Although extreme hypoxic conditions may compromise the health of

Although extreme hypoxic conditions may compromise the health of the cells and lead to cell death, similar con fluencies between the normoxic and hypoxic condition at the conclusion of testing suggest that the 48 hour incuba tion prior to testing was sufficient U0126 order for cell adherence and equilibration. To support this observation, Pilch et al. found that hypoxia did not cause cell death decreased confluency, as dead cells were not observed in supernatant post hypoxia. Furthermore, Inhibitors,Modulators,Libraries the hypoxic oxygen concentration used in the study in vitro is similar to that reported by Hockel and Vaupel, Inhibitors,Modulators,Libraries 2001, in the core of solid tumors in vivo. Also, in addition to the 11 angiogenesis related analytes chosen for testing, a negative control unrelated to angio genesis was also assessed.

A chemotactic cytokine, RANTES, is responsible for recruiting leukocytes and acti vating natural killer cells. This cytokine was not expected to vary in a normoxic versus hypoxic environ ment, and we found similar expression levels of RANTES for both conditions validating our technical Inhibitors,Modulators,Libraries approach. Multiple techniques are available to assess VEGF expres sion. Some laboratories employ Inhibitors,Modulators,Libraries immunohistochemical analysis to determine VEGF receptor levels, usu ally for diagnostic and prognostic purposes. However, this study employed the Beadlyte CytokineProfiler Testing Service for two reasons. First, Inhibitors,Modulators,Libraries this service provides quanti tative analysis of the expression levels of the angiogenesis related factors, including VEGF. Second, testing was per formed on malignant epithelial cell cultures, rather than tissue sections.

Intact tissue sections that contain tumor CB-7598 cells as well as support tissue and vasculature are generally stained using IHC. VEGF receptors on endothelial cells and monocytes fluoresce. The described culture process selects specifically for malignant epithelial cells. Endothelial cells are selected against by culture condi tions, as the media employed do not promote the growth of these cells. monocytes are non adherent, so are rinsed away in routine media changes. Neither of these cell types is present in the described samples so IHC of the VEGF receptors was not possible. VEGF production was of most interest to this study due to its role in the mechanism of action of bevacizumab. The testing conditions were optimized to ensure that VEGF production was measurable, so VEGF results were availa ble for all samples tested. Table 3 includes the summary of all data in the All Samples field, a total of 50 samples. Results for the other ten analytes had detection levels out of range of the standard curve for at least two samples, if not more. As a result, the sample size for most of these angiogenesis related factors was less than 50.

Our ana lysis indicates

Our ana lysis indicates Crenolanib msds that, despite these structural rearrange ments, the three regions have retained their nuclear neighbourhood. This observation corroborates findings of evolutionarily conserved principles of nuclear organ isation at the resolution of interphase FISH and is in line with a recent report on an increased Hi C inter action probability Inhibitors,Modulators,Libraries between murine syntenic breakpoint regions on human chromosomes, a phenomenon which has been termed spatial synteny. As a consequence of spatial synteny, SD paralogs that are separated by structural rearrangements and appear distant on the linear chromosome are still in close spatial proximity in the interphase nucleus.

A possible role for SDs in spatial Inhibitors,Modulators,Libraries synteny In light of the observed conservation of nuclear archi tecture, we have asked what factors could Inhibitors,Modulators,Libraries account for spatial synteny and whether the biased distribution of SDs might play a role therein and in nuclear organisa tion in general. It is still unclear whether nuclear architecture Inhibitors,Modulators,Libraries is determined by a nuclear scaffold or rep resents the outcome of self organisation choreographed by intrinsic properties of the chromatin itself, or a combination thereof. Although several DNA protein interactions and epigenetic marks clearly correlate with specific features of chromatin organisation, DNA se quence by itself is likely to play a crucial role. One DNA sequence feature significantly enriched in those segments of chromosome 7 that are syntenic to a large block of marmoset chromosome 2 are G4 DNA motifs.

These motifs can establish highly stable intramolecular and inter molecular connections via Hoogsteen pairing between four guanines and have already been implicated in telo Inhibitors,Modulators,Libraries mere organisation and in meiotic chromosome pairing. The non random distribution of G4 motifs along human chromosome 7, as shown in this study, could point selleck screening library at a possible function of quadruplex structures in the re tention of spatial proximities also in interphase nuclei. High frequency of Alu repeats is another, partly interre lated, sequence feature that we have found significantly enriched in these highly interacting regions. Alu repeat distribution is not the result of regional insertion preferences, but more likely the consequence of selective pressure on GC content biased removal. Against this background, Alu repeats have been impli cated in higher order chromatin organisation. However, the overall presence of both Alu repeats and G4 motifs throughout the genome raises the question how such a sequence directed organisation of the nu cleus might obtain its specificity in the first place.