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Interplay of transcriptomics and proteomics.

Despite the obvious attractions of parallel profiling of transcripts and proteins on a global 'omic' scale, there are practical and biological differences involved in their application. Transcriptomics is now a robust, high-throughput, cost-effective technology capable of simultaneously quantifying tens of thousands of defined mRNA species in a miniaturized, automated format. Conversely, proteomic analysis is currently much more limited in breadth and depth of coverage owing to variations in protein abundance, hydrophobicity, stability, size and charge. Nevertheless, transcriptomic and proteomic data can be compared and contrasted provided the studies are carefully designed and interpreted. Differential splicing, post-translational modifications and data integration are among some of the future challenges to tackle.

Biotechnology↗

Interplay of pu.1 and gata1 determines myelo-erythroid progenitor cell fate in zebrafish.

The zebrafish is a powerful model system for investigating embryonic vertebrate hematopoiesis, allowing for the critical in vivo analysis of cell lineage determination. In this study, we identify zebrafish myeloerythroid progenitor cells (MPCs) that are likely to represent the functional equivalent of mammalian common myeloid progenitors. Utilizing transgenic pu.1-GFP fish, real-time MPC differentiation was correlated with dynamic changes in cell motility, morphology, and gene expression. Unlike mammalian hematopoiesis, embryonic zebrafish myelopoiesis and erythropoiesis occur in anatomically separate locations. Gene knockdown experiments and transplantation assays demonstrated the reciprocal negative regulation of pu.1 and gata1 and their non-cell-autonomous regulation that determines myeloid versus erythroid MPC fate in the distinct blood-forming regions. Furthermore, forced expression of pu.1 in the bloodless mutant cloche resulted in myelopoietic rescue, providing intriguing evidence that this gene can function in the absence of some stem cell genes, such as scl, in governing myelopoiesis.

Animals↗

Interplay between chromatin and cell cycle checkpoints in the context of ATR/ATM-dependent checkpoints.

Maintenance of both genome stability and its structural organization into chromatin are essential to avoid aberrant gene expression that could lead to neoplasia. Genome integrity being threatened by various sources of genotoxic stresses, cells have evolved regulatory mechanisms, termed cell cycle checkpoints. In general, these surveillance pathways are thought to act mainly to coordinate proficient DNA repair with cell cycle progression. To date, this cellular response to genotoxic stress has been viewed mainly as a DNA-based signal transduction pathway. Recent studies, in both yeast and human, however, highlight possible connections between chromatin structure and cell cycle checkpoints, in particular those involving kinases of the ATM and ATR family, known as key response factors activated early in the checkpoint pathway. In this review, based on this example, we will discuss hypotheses for chromatin-based events as potential initiators of a checkpoint response or conversely, for chromatin-associated factors as targets of checkpoint proteins, promoting changes in chromatin structure, in order to make a lesion more accessible and contribute to a more efficient repair response.

Animals↗

The interplay of Fanconi anemia proteins in the DNA damage response.

Fanconi anemia (FA) is a rare autosomal recessive disease characterized by chromosome instability and cancer predisposition. At least 11 complementation groups for FA have been identified, and eight FA genes have been cloned. Interestingly, the eight known FA proteins cooperate in a common pathway leading to the interaction of monoubiquitinated FANCD2 and BRCA2 in damaged chromatin. Disruption of this pathway results in the clinical and cellular abnormalities common to all FA subtypes. This review will examine the interaction of the cloned FA proteins with each other and with other DNA damage response proteins (i.e., ATM, ATR, and NBS1). Also, somatic (acquired) disruption of the FA pathway in human tumors appears to account for their chromosome instability and crosslinker hypersensitivity.

Ataxia Telangiectasia Mutated Proteins↗

The interplay between help-seeking and alcohol-related outcomes: divergent processes for professional treatment and self-help groups.

This study examined the influence of self-selection, as reflected in alcohol-related functioning, on the duration of professional treatment and Alcoholics Anonymous (AA), and the influence of social causation, as reflected in the duration of treatment and AA, on alcohol-related outcomes. A sample of alcoholic individuals was surveyed at baseline and 1, 3, and 8 years later. At each point, participants completed an inventory that assessed participation in treatment and AA since the last assessment and alcohol-related functioning. There were divergent processes of self-selection and social causation with respect to the duration of participation in professional treatment and AA. Individuals with more severe alcohol-related problems obtained longer episodes of professional treatment, but this self-selection process was much less evident for AA. Longer participation in professional treatment in the first year predicted better alcohol-related outcomes; however, the duration of subsequent treatment was not associated with better subsequent outcomes. In contrast, longer participation in AA consistently predicted better subsequent alcohol-related outcomes. These findings are consistent with a need-based model of professional treatment, in which more treatment is selected by and allocated to individuals with more severe problems, and an egalitarian model of self-help, in which need factors play little or no role in continued participation.

Adult↗

The role of the bone microenvironment in the pathophysiology and therapeutic management of multiple myeloma: interplay of growth factors, their receptors and stromal interactions.

The close relationship between the biological behaviour of malignant cells and the local microenvironment where they reside is a feature of diverse neoplasias. Multiple myeloma (MM) is considered a main disease model for the study of such interactions and the mechanisms that can lead to bone-related clinical complications, as well as the role of these interactions in attenuating the activity of conventional anti-MM therapeutics, such as dexamethasone and cytotoxic chemotherapeutics. This review focuses on recent progress in the study of interactions of MM cells with their local microenvironment. Major emphasis is placed on how bone marrow stromal cells (BMSCs) and other normal constituents of the bone marrow milieu promote, through cell adhesion- and cytokine-mediated mechanisms, the ability of MM cells to resist conventional anti-MM therapies. The review also addresses ongoing research into these mechanisms, which has already provided several new molecular targets and corresponding therapeutic strategies, such as the proteasome inhibitor bortezomib and thalidomide derivatives (e.g. lenalidomide), for the management of myeloma.

Bone Diseases↗

Thoracoabdominal aortic aneurysm repair: interplay of spinal cord protecting modalities.

BACKGROUND: The purpose of this study was to assess the complementary use of different methods of measuring spinal cord perfusion during thoracoabdominal aortic surgery. METHODS: The spinal cords of 28 patients undergoing surgery on the thoracoabdominal aorta were monitored with transcranial electrical stimulation (tcMEP) and somatosensory-evoked potentials (SSEP). Available approaches of spinal cord-protection included: Moderate systemic hypothermia, constant cerebrospinal fluid (CSF) drainage and pressure monitoring, reimplantation of segmental arteries, cardiopulmonary bypass (CPB), and staged clamping. RESULTS: Fourteen of 19 patients (75%) undergoing open surgical treatment (Group I) exhibited loss of tcMEP after proximal aortic clamping. In nine cases (47%), we observed recovery of tcMEP after intraoperative interventions, while two patients subsequently developed paraplegia and three died. Seventeen of 19 patients showed loss of SSEP, with recovery in 12 cases (63%). During stent-graft implantation (Group II), one of nine patients (11%) demonstrated tcMEP loss with intraoperative, intervention-related recovery. The SSEP-recording course remained stable. CONCLUSIONS: tcMEP/SSEP monitoring has proved to be an excellent means of detecting spinal cord ischaemia during surgery on thoracoabdominal aortic aneurysms. The prognostic value of tcMEP monitoring should be considered superior to that of SSEP measurements, because of its direct and rapid response to spinal malperfusion. Through combined neurophysiological monitoring, vital parameter balancing and intraoperative interventions, spinal cord perfusion improves and recovery of tcMEP and SSEP is achievable, reducing the prevalence of postoperative paraplegia.

Adult↗

Mucosal interplay among commensal and pathogenic bacteria: lessons from flagellin and Toll-like receptor 5.

Toll-like receptors (TLR) detect pathogen-associated molecular patterns (PAMP) and play a crucial role in triggering immunity. Due to their large surfaces in direct contact with the environment, mucosal tissues are the major sites of PAMP-TLR signalling. How innate and adaptive immunity are triggered through flagellin-TLR5 interaction is the main focus of the review. In view of recent reports on genetic polymorphism, we will summarize the impact of TLR5 on the susceptibility to mucosal infections and on various immuno-pathologies. Finally, the contribution of TLRs in the induction and maintenance of mucosal homeostasis and commensal discrimination is discussed.

Bacterial Physiological Phenomena↗

On the interplay of gene positioning and the role of rho-independent terminators in Escherichia coli.

The majority of intrinsic rho-independent terminator signals, reported to consist of stable hairpin structures followed by T-rich regions, possess the potential to operate bi-directionally and to induce transcription terminations on both strands of the DNA duplex in Escherichia coli. By using RNAMotif software, we investigated the distributions of termination motifs around the 3'-ends of overlapping and non-overlapping genes at the genomic level. We suggest that the positions of compactly encoded E. coli genes and rho-independent terminators are optimized to terminate the adjoining genes on their antisense strands efficiently, and not to mis-terminate overlapping transcripts, due to their bi-directional properties.

Escherichia coli↗

Interplay between maternal weight and seasons in determining the secondary sex ratio of human offspring.

When gender of 9,284 single fetuses, which were delivered at term in the Policlinic of Modena between 1997-2001, was stratified for month of conception and for quartiles of pregravid maternal weight, it showed that the ratio of male to female fetuses (secondary sex ratio) was characterized by a clear seasonal variation that was modulated by pregravid maternal weight. Two seasonal peaks of sex ratio (March and October +/- 31 days) were observed in mothers in the lowest two quartiles of prepregnancy body weight (< or =62 kg), and one single peak (October +/-36 days) was observed in mothers with preconception weight in the upper two quartiles.

Adult↗

Interplay of mechanical deformation and patterned gene expression in developing embryos.

The shaping of the early embryo requires pattern formation as well as geometric and topological morphogenesis of the developing tissues. The morphogenetic movements that lead to geometric shape changes are controlled by patterned gene expression. How particular movements are related to patterning genes, and which underlying molecular and cellular mechanisms lead to coordinated macroscopic movements that induce morphogenesis, remain the challenging questions of embryonic development. How morphogenetic movements could modulate the expression of developmental genes is an emerging question, potentially opening new horizons in developmental biology. This question instigates the task of characterizing the molecular and cellular mechanisms underlying these mechano-transcription events.

Animals↗

Chloroplast membrane transport: interplay of prokaryotic and eukaryotic traits.

Chloroplasts are specific plant organelles of prokaryotic origin. They are separated from the surrounding cell by a double membrane, which represents an effective barrier for the transport of metabolites and proteins. Specific transporters in the inner envelope membrane have been described, which facilitate the exchange of metabolites. In contrast, the outer envelope has been viewed for a long time as a molecular sieve that offers a mere size constriction to the passage of molecules. This view has been challenged lately, and a number of specific and regulated pore proteins of the outer envelope (OEPs) have been identified. These pores seem to have originated by adaptation of outer membrane proteins of the cyanobacterial ancestor of the chloroplast. In a similar fashion, the transport of proteins across the two envelope membranes is achieved by two hetero-oligomeric protein complexes called Toc (translocon in the outer envelope of chloroplasts) and Tic (translocon in the inner envelope of chloroplasts). The phylogenetic provenance of the translocon components is less clear, but at least the channel protein of the Toc translocon is of cyanobacterial origin. Characteristic of cyanobacteria and chloroplasts is furthermore a specialized internal membrane system, the thylakoids, on which the components of the photosynthetic machinery are located. Despite the importance of this membrane, very little is known about its phylogenetic origin or the manner of its synthesis. Vipp1 appears to be a ubiquitous component of thylakoid formation, while in chloroplasts of land plants, additionally a vesicle transport system of eukaryotic origin might be involved in this process.

Biological Evolution↗

Concert of regulators to switch on LEE expression in enterohemorrhagic Escherichia coli O157:H7: interplay between Ler, GrlA, HNS and RpoS.

Enterohemorrhagic (EHEC) and enteropathogenic (EPEC) Escherichia coli strains carry a pathogenicity island termed locus of enterocyte effacement (LEE) responsible for attaching and effacing lesions on epithelial cells. The expression of LEE varies among isolates and is dependent on environmental cues. In the EHEC O157:H7 Sakaï isolate (RIMD-0509952 strain), we found that the non-coding RNA, DsrA, activates the expression of the LEE. This activation requires RpoS, the stress sigma factor. The DsrA/RpoS regulatory pathway mediates its positive effect by stimulating the transcription of ler, a positive regulatory gene encoded by the LEE. A second regulatory pathway, repressed by HNS, is also able to activate the transcription of ler and requires GrlA, another LEE-encoded regulator. Both regulatory pathways, DsrA/RpoS and HNS/GrlA, affect the activity of the ler distal promoter and require the Ler protein to be functional. Our data demonstrate that the LEE expression can be turned on by at least two separate pathways acting on the transcription of ler.

Bacterial Proteins↗

MHC II molecules in inflammatory diseases: interplay of qualities and quantities.

It is generally accepted that MHC II molecules confer susceptibility to inflammatory diseases because of the different abilities they possess for binding and presenting peptides to T cells. A new study suggests that the level of MHC II gene expression is also a risk factor for such diseases. It shows that a polymorphism in the promoter of the MHC II transactivator (MHC2TA) gene (which encodes CIITA), leads to reduced MHC2TA expression, and hence reduced production of MHC II molecules. This predisposes to rheumatoid arthritis, multiple sclerosis and myocardial infarction.

Arthritis, Rheumatoid↗

Adhesion as an interplay between particle size and surface roughness.

Surface roughness plays an important role in the adhesion of small particles. In this paper we have investigated adhesion as a geometrical effect taking into account both the particle size and the size of the surface features. Adhesion is studied using blunt model particles on surfaces up to 10 nm root-mean-square (RMS) roughness. Measurements with particles both smaller and larger than surface features are presented. Results indicate different behavior in these areas. Adhesion of particles smaller than or similar in size to the asperities depend mainly on the size and shape of the asperities and only weakly on the size of the particle. For large particles also the particle size has a significant effect on the adhesion. A new model, which takes the relative size of particles and asperities into account, is also derived and compared to the experimental data. The proposed model predicts adhesion well over a wide range of particle/asperity length scales.

Journal Article↗

The interplay between perceptual organization and categorization in the representation of complex visual patterns by young infants.

The relation between perceptual organization and categorization processes in 3- and 4-month-olds was explored. The question was whether an invariant part abstracted during category learning could interfere with Gestalt organizational processes. A 2003 study by Quinn and Schyns had reported that an initial category familiarization experience in which infants were presented with visual patterns consisting of a pacman shape and a complex polygon could interfere with infants' subsequent good continuation-based parsing of a circle from visual patterns consisting of a circle and a complex polygon. However, an alternative noninterference explanation for the results was possible because the pacman had been presented with greater frequency and duration than had the circle. The current study repeated Quinn and Schyns's procedure but provided an equivalent number of familiarization trials and duration of study time for the infants to process the pacman during initial familiarization and the circle during subsequent familiarization. The results replicated the previous findings of Quinn and Schyns. The data are consistent with the interference account and suggest that a cognitive system of adaptable feature creation can take precedence over organizational principles with which a perceptual system comes pre-equipped.

Cognition↗