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FMI
Helsinki, Finland

Keckhut P.,French National Center for Scientific Research | Hauchecorne A.,French National Center for Scientific Research | Blanot L.,ACRI ST | Hocke K.,University of Bern | And 6 more authors.
Atmospheric Chemistry and Physics | Year: 2010

The GOMOS ozone profiles have been analysed to evaluate the GOMOS ability to capture the long-term ozone evolution at mid-latitudes during the expected recovery phase of the ozone layer. Version 5 of the operational GOMOS ozone data has been compared with data from two of the longest ground-based instruments based on different techniques and already involved with many other previous space instrument validations. Comparisons between ground-based and GOMOS data confirm the occurrence of spurious retrievals mainly occurring since 2006. Using a selected set of data it is shown that some bad retrievals are induced by the increasing dark charge of the detectors combined with an inadequate method for its correction. This effect does not only induce a continuous bias, but is rather exhibiting a bimodal distribution including the correct profiles and the bad retrievals. For long-term analyses it is recommended filtering the data according to background light conditions and star temperature (spectrum shape). The new method of the dark charge estimate proposed to be implemented in the version 6 of the ESA algorithm seems to significantly reduce the occurrence of such effects and should allow to monitor stratospheric ozone using GOMOS data with greater confidence. © 2010 Author(s).


News Article | December 16, 2015
Site: phys.org

In a study published in Nature, Dirk Schübeler and his group at the Friedrich Miescher Institute for Biomedical Research (FMI) describe how the interplay between transcription factors and epigenetic modifications of DNA influences gene regulation. The scientists found that transcription factors can cooperate indirectly, via changes in DNA methylation patterns: by removing methyl groups, some transcription factors prepare surrounding regions for the binding of other transcription factors. This research thus elucidates a further aspect of the complex role methyl groups play in gene regulation.


News Article
Site: www.rdmag.com

Fluid Metering Inc. has introduced the PDS-100 Programmable Dispenser for battery manufacturing process applications requiring precision, maintenance-free fluid control. The PDS-100 is designed for dispensing and metering electrolytes, slurries and metal forming lubricants used in the manufacture of AA, AAA, C, D and button cell batteries. The PDS-100 integrates FMI’s patented CeramPump design with precision programmable stepper motor control. The pump electronics are housed in a rugged anodized aluminum enclosure suitable for desktop or wall mounting and features intuitive front panel programming of dispense and continuous metering modes. The PDS-100 is available in both single- and dual-pump head configurations. For duplex configurations, the displacement and speed of each pump head can be individually controlled, suitable for proportional mixing and diluting. Duplex configurations can also provide economic two-channel dispensing, effectively doubling production capacity at a fraction of the cost of using two individual dispensers. The PDS-100 utilizes Fluid Metering’s patented CeramPump pumping principle. One moving part, a rotating and reciprocating ceramic piston, accomplishes all fluid control functions in the pump, thereby eliminating check valves and their associated failure and maintenance issues. It will dispense from 2 uL/min up to 1 L/min continuous metering, while maintaining a precision of 0.5% for millions of dispenses without re-calibration or downtime.


News Article
Site: phys.org

A better knowledge of RNA metabolism is key to understanding how RNAs regulate development and differentiation, and how their malfunction leads to disease. A team led by Helge Grosshans of the Friedrich Miescher Institute for Biomedical Research (FMI) has now identified a novel and evolutionarily conserved mechanism that preserves the stability of RNases and keeps them poised for RNA processing and degradation. The results have been published in Nature Structural & Molecular Biology. For many decades, scientists thought that RNA functions merely as an intermediary between DNA and proteins. However, it has now become evident that RNA occurs in many flavors in the cell, allowing it to perform diverse and important functions. In addition to serving as a photocopy of DNA, a coupler between the genetic code and protein building blocks, and a structural component of ribosomes (the protein-producing machines), RNAs also directly regulate gene activity during development and differentiation. Accordingly, RNA malfunction has been implicated in numerous diseases, and research into RNA metabolism – the processes whereby RNA is formed, processed and degraded – has gained momentum. RNases (ribonucleases) are key enzymes in RNA metabolism, as they can chew up RNAs partially or completely, thus causing either RNA maturation from precursors or inactivation by degradation. However, it has remained unclear how RNase activity is controlled. Helge Grosshans and his group at the FMI have now identified a mechanism – conserved between the roundworm C. elegans and higher vertebrates – that preserves the stability of RNases in the absence of substrate. In a paper published in Nature Structural & Molecular Biology, they describe how an RNase forms a complex with a protein partner, and how this complex formation prevents inactivation of the RNase. As a first step, Hannes Richter, a PhD student in the Grosshans laboratory, collaborated with a colleague from FMI's protein structure facility to elucidate the structure of a complex of the C. elegans RNase XRN2 and its partner PAXT-1. Richter, first author of the study, comments: "Our previous biochemical experiments already suggested that PAXT-1 interacted with XRN2 through its N-terminus. The crystal structure of XRN2 bound to PAXT-1 confirmed this: there are several amino acid residues in the N-terminus of PAXT-1 that mediate binding to XRN2. However, one amino acid in PAXT-1, Tyr56, is particularly important. When it is changed, the whole complex falls apart." In collaboration with a scientist from FMI's C. elegans facility, Richter showed that worms with a mutation in this tyrosine had the same symptoms as worms lacking PAXT-1 altogether. Interestingly, the XRN2-binding domain (XTBD) also occurs in other vertebrate proteins which, apart from this domain, share little homology to PAXT-1. "The critical residue is highly conserved," says Richter. With this in mind, the scientists investigated whether three vertebrate proteins with XTBDs also interacted with XRN2 and could even functionally replace PAXT-1 in the worm. Richter reports: "The function of the XTB domain is indeed conserved: vertebrate XTBD-containing proteins bind to XRN2 in vitro, and a human XTBD protein rescued worms lacking PAXT-1." But how does PAXT-1 binding to an RNase affect RNA metabolism? In a set of biochemical experiments, the scientists showed that PAXT-1 stabilizes XRN2 and preserves its activity in the absence of RNA. Grosshans notes: "This is something new – we tend to think of enzyme complexes as something that alters the activity of enzymes on their substrates. Here we find that PAXT-1 takes care of 'idle' XRN2 molecules, preventing them from going out of shape. This ensures that there is a constant pool of active RNases in the cell, poised for further action." Explore further: A macromolecular shredder for RNA: Researchers unravel the structure of the machinery for RNA disposal More information: Hannes Richter et al. Structural basis and function of XRN2 binding by XTB domains, Nature Structural & Molecular Biology (2016). DOI: 10.1038/nsmb.3155


Despite the fact that our genes are physically very dynamic, shifting rapidly and randomly within the interphase nucleus, there are also subnuclear compartments in which genes are sequestered when they are inactive and other zones that harbor genes which are likely to be expressed. Whether this sub-compartmentalization happens by chance or whether the inactive DNA is indeed intentionally packed away has remained unclear. Even more significantly, the importance of the observed 3D organization for cell fate decisions and the development of the organism has stayed elusive. Adriana Gonzalez-Sandoval, a PhD student in Susan Gasser's group at the Friedrich Miescher Institute for Biomedical Research (FMI), has exploited a genetic screen in C. elegans based on fluorescence microscopy, to identify a protein that anchors inactive DNA to the inner face of the nuclear envelope. The factor is a previously uncharacterized C. elegans chromodomain protein (CEC-4), which associates stably with the nuclear membrane and binds chromatin containing methylated H3K9– which is either inactive or on the way to becoming inactive. "This is the anchor that the community has been looking for a long time," commented Gasser. "Our findings show for the first time that there is indeed a specific molecular mechanism in place that leads to the observed nuclear organization of inactive chromatin. It does not happen by chance. The characterization of this protein was only possible thanks to the amazing people in FMI facilities and our C-NIBR collaborators." But as is often the case in science, this long sought-after player in nuclear organization did not act as expected. "We were extremely surprised to see that under normal growth conditions transcription did not change in the absence of this anchor," commented Gonzalez-Sandoval. "Even though the protein existed and clearly anchored heterochromatin to the nuclear periphery, it did not matter: Without CEC-4 the worms developed normally, the necessary genes were transcribed, and inactive genes were left untouched. We were left wondering, what is this anchor good for?" Well, order—or as the proverb says, "a place for everything and everything in its place"—is most useful under conditions of perturbation or stress. Indeed, in a second set of experiments, Gonzalez-Sandoval showed that CEC-4 stabilizes development when the worm embryos are forced to differentiate into muscle. The scientists found that anchoring chromatin contributes to the robust maintenance of an induced muscle differentiation program and the suppression of other cell fates. "This was a puzzling result at first, but given the biological context, it rather reveals a basic tenet of how the spatial segregation of genes contributes to differentiation," commented Gasser. "Instead of driving differentiation, sequestration "keeps things on track" and helps restrict the outcome of induction to only muscle genes." While there is no obvious impact on development under standard laboratory conditions, by perturbing development at the right stage, the scientists were able to reveal the contribution that nuclear anchoring makes towards stabilizing cell fate decisions. "Although in many ways unexpected, our results provide a compelling insight: They allowed us to separate positioning from repression and helped us establish a new paradigm for the contribution of nuclear anchoring towards the stabilization of cell fate decisions," commented Gasser. "And although the findings are based on C. elegans, the histone marks implicated are conserved as is the phenomenon of tissue specific heterochromatin sequestration at the nuclear envelope." Explore further: The role of H3K9 in bringing order to the nucleus More information: Adriana Gonzalez-Sandoval et al. Perinuclear Anchoring of H3K9-Methylated Chromatin Stabilizes Induced Cell Fate in C. elegans Embryos, Cell (2015). DOI: 10.1016/j.cell.2015.10.066

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