Fractional anisotropy in white matter tracts of very-low-birth-weight infants

Background: Advances in neonatal intensive care have not yet reduced the high incidence of neurodevelopmental disability among very-low-birth-weight (VLBW) infants. As neurological deficits are related to white-matter injury, early detection is important. Diffusion tensor imaging (DTI) could be an excellent tool for assessment of white-matter injury. Objective: To provide DTI fractional anisotropy (FA) reference values for white-matter tracts of VLBW infants for clinical use. Materials and methods: We retrospectively analysed DTI images of 28 VLBW infants (26-32 weeks gestational age) without evidence of white-matter abnormalities on conventional MRI sequences, and normal developmental outcome (assessed at age 1-3 years). For DTI an echoplanar sequence with diffusion gradient (b = 1,000 s/mm2) applied in 25 non-collinear directions was used. We measured FA and apparent diffusion coefficient (ADC) of different white-matter tracts in the first 4 days of life. Results: A statistically significant correlation was found between gestational age and FA of the posterior limb of the internal capsule in VLBW infants (r = 0.495, P<0.01). Conclusion: Values of FA and ADC were measured in white-matter tracts of VLBW infants. FA of the pyramidal tracts measured in the first few days after birth is related to gestational age

The E. coli Anti-Sigma Factor Rsd: Studies on the Specificity and Regulation of Its Expression

Background: Among the seven different sigma factors in E. coli s 70 has the highest concentration and affinity for the core RNA polymerase. The E. coli protein Rsd is regarded as an anti-sigma factor, inhibiting s 70-dependent transcription at the onset of stationary growth. Although binding of Rsd to s 70 has been shown and numerous structural studies on Rsd have been performed the detailed mechanism of action is still unknown. Methodology/Principal Findings: We have performed studies to unravel the function and regulation of Rsd expression in vitro and in vivo. Cross-linking and affinity binding revealed that Rsd is able to interact with s 70, with the core enzyme of RNA polymerase and is able to form dimers in solution. Unexpectedly, we find that Rsd does also interact with s 38, the stationary phase-specific sigma factor. This interaction was further corroborated by gel retardation and footprinting studies with different promoter fragments and s 38-ors 70-containing RNA polymerase in presence of Rsd. Under competitive in vitro transcription conditions, in presence of both sigma factors, a selective inhibition of s 70-dependent transcription was prevailing, however. Analysis of rsd expression revealed that the nucleoid-associated proteins H-NS and FIS, StpA and LRP bind to the regulatory region of the rsd promoters. Furthermore, the major promoter P2 was shown to be down-regulated in vivo by RpoS, the stationary phase-specific sigma factor and the transcription factor DksA, while induction of the stringent control enhanced rsd promoter activity. Most notably, the dam-dependent methylation of a cluster of GATC sites turned ou

Phage-Induced Expression of CRISPR-Associated Proteins Is Revealed by Shotgun Proteomics in Streptococcus thermophilus

The CRISPR/Cas system, comprised of clustered regularly interspaced short palindromic repeats along with their associated (Cas) proteins, protects bacteria and archaea from viral predation and invading nucleic acids. While the mechanism of action for this acquired immunity is currently under investigation, the response of Cas protein expression to phage infection has yet to be elucidated. In this study, we employed shotgun proteomics to measure the global proteome expression in a model system for studying the CRISPR/Cas response in S. thermophilus DGCC7710 infected with phage 2972. Host and viral proteins were simultaneously measured following inoculation at two different multiplicities of infection and across various time points using two-dimensional liquid chromatography tandem mass spectrometry. Thirty-seven out of forty predicted viral proteins were detected, including all proteins of the structural virome and viral effector proteins. In total, 1,013 of 2,079 predicted S. thermophilus proteins were detected, facilitating the monitoring of host protein synthesis changes in response to virus infection. Importantly, Cas proteins from all four CRISPR loci in the S. thermophilus DGCC7710 genome were detected, including loci previously thought to be inactive. Many Cas proteins were found to be constitutively expressed, but several demonstrated increased abundance following infection, including the signature Cas9 proteins from the CRISPR1 and CRISPR3 loci, which are key players in the interference phase of the CRISPR/Cas response. Altogether, these results provide novel insights into the proteomic response of S. thermophilus, specifically CRISPR-associated proteins, upon phage 2972 infection

Curriculum vitae of the LOTOS–EUROS (v2.0) chemistry transport model

The development and application of chemistry transport models has a long tradition. Within the Netherlands the LOTOS–EUROS model has been developed by a consortium of institutes, after combining its independently developed predecessors in 2005. Recently, version 2.0 of the model was released as an open-source version. This paper presents the curriculum vitae of the model system, describing the model's history, model philosophy, basic features and a validation with EMEP stations for the new benchmark year 2012, and presents cases with the model's most recent and key developments. By setting the model developments in context and providing an outlook for directions for further development, the paper goes beyond the common model description. With an origin in ozone and sulfur modelling for the models LOTOS and EUROS, the application areas were gradually extended with persistent organic pollutants, reactive nitrogen, and primary and secondary particulate matter. After the combination of the models to LOTOS–EUROS in 2005, the model was further developed to include new source parametrizations (e.g. road resuspension, desert dust, wildfires), applied for operational smog forecasts in the Netherlands and Europe, and has been used for emission scenarios, source apportionment, and long-term hindcast and climate change scenarios. LOTOS–EUROS has been a front-runner in data assimilation of ground-based and satellite observations and has participated in many model intercomparison studies. The model is no longer confined to applications over Europe but is also applied to other regions of the world, e.g. China. The increasing interaction with emission experts has also contributed to the improvement of the model's performance. The philosophy for model development has always been to use knowledge that is state of the art and proven, to keep a good balance in the level of detail of process description and accuracy of input and output, and to keep a good record on the effect of model changes using benchmarking and validation. The performance of v2.0 with respect to EMEP observations is good, with spatial correlations around 0.8 or higher for concentrations and wet deposition. Temporal correlations are around 0.5 or higher. Recent innovative applications include source apportionment and data assimilation, particle number modelling, and energy transition scenarios including corresponding land use changes as well as Saharan dust forecasting. Future developments would enable more flexibility with respect to model horizontal and vertical resolution and further detailing of model input data. This includes the use of different sources of land use characterization (roughness length and vegetation), detailing of emissions in space and time, and efficient coupling to meteorology from different meteorological models

Air pollution trends in the EMEP region between 1990 and 2012

The present report synthesises the main features of the evolution over the 1990-2012 time period of the concentration and deposition of air pollutants relevant in the context of the Convention on Long-range Transboundary Air Pollution: (i) ozone, (ii) sulfur and nitrogen compounds and particulate matter, (iii) heavy metals and persistent organic pollutants. It is based on observations gathered in State Parties to the Convention within the EMEP monitoring network of regional background stations, as well as relevant modelling initiatives. Joint Report of: EMEP Task Force on Measurements and Modelling (TFMM), Chemical Co-ordinating Centre (CCC), Meteorological Synthesizing Centre-East (MSC-E), Meteorological Synthesizing Centre-West (MSC-W)

Balancing the immune response in the brain: IL-10 and its regulation

Background: The inflammatory response is critical to fight insults, such as pathogen invasion or tissue damage, but if not resolved often becomes detrimental to the host. A growing body of evidence places non-resolved inflammation at the core of various pathologies, from cancer to neurodegenerative diseases. It is therefore not surprising that the immune system has evolved several regulatory mechanisms to achieve maximum protection in the absence of pathology. Main body: The production of the anti-inflammatory cytokine interleukin (IL)-10 is one of the most important mechanisms evolved by many immune cells to counteract damage driven by excessive inflammation. Innate immune cells of the central nervous system, notably microglia, are no exception and produce IL-10 downstream of pattern recognition receptors activation. However, whereas the molecular mechanisms regulating IL-10 expression by innate and acquired immune cells of the periphery have been extensively addressed, our knowledge on the modulation of IL-10 expression by central nervous cells is much scattered. This review addresses the current understanding on the molecular mechanisms regulating IL-10 expression by innate immune cells of the brain and the implications of IL-10 modulation in neurodegenerative disorders. Conclusion: The regulation of IL-10 production by central nervous cells remains a challenging field. Answering the many remaining outstanding questions will contribute to the design of targeted approaches aiming at controlling deleterious inflammation in the brain.We acknowledge the Portuguese Foundation for Science and Technology (FCT) for providing a PhD grant to DLS (SFRH/BD/88081/2012) and a post-doctoral fellowship to SR (SFRH/BPD/72710/2010). DS, AGC and SR were funded by FEDER through the Competitiveness Factors Operational Programme (COMPETE) and National Funds through FCT under the scope of the project POCI-01-0145-FEDER007038; and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The MS lab was financed by Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT in the framework of the project “Institute for Research and Innovation in Health Sciences ” (POCI-01-0145-FEDER-007274). MS is a FCT Associate Investigator. The funding body had no role in the design of the study and collection, analysis, and interpretation of the data and in writing the manuscript

Clinical Use and Therapeutic Potential of IVIG/SCIG, Plasma-Derived IgA or IgM, and Other Alternative Immunoglobulin Preparations

Intravenous and subcutaneous immunoglobulin preparations, consisting of IgG class antibodies, are increasingly used to treat a broad range of pathological conditions, including humoral immune deficiencies, as well as acute and chronic inflammatory or autoimmune disorders. A plethora of Fab- or Fc-mediated immune regulatory mechanisms has been described that might act separately or in concert, depending on pathogenesis or stage of clinical condition. Attempts have been undertaken to improve the efficacy of polyclonal IgG preparations, including the identification of relevant subfractions, mild chemical modification of molecules, or modification of carbohydrate side chains. Furthermore, plasma-derived IgA or IgM preparations may exhibit characteristics that might be exploited therapeutically. The need for improved treatment strategies without increase in plasma demand is a goal and might be achieved by more optimal use of plasma-derived proteins, including the IgA and the IgM fractions. This article provides an overview on the current knowledge and future strategies to improve the efficacy of regular IgG preparations and discusses the potential of human plasma-derived IgA, IgM, and preparations composed of mixtures of IgG, IgA, and IgM

Ammoniakdepositie in de duinen langs de Noordzee- en Waddenzeekust : Analyse van het verschil tussen gemeten en met OPS gemodelleerde concentraties

Nederland kent een hoge uitstoot van stikstofverbindingen, waardoor stikstofdepositie een grote bedreiging vormt voor de Nederlandse natuur. Gebleken is dat de gemeten ammoniakconcentraties in de natuur langs de kust systematisch hoger liggen dan de modelberekeningen ('duinengat'). Hoewel de gemeten ammoniakconcentraties nog altijd laag zijn ten opzichte van andere delen van Nederland, treedt in de gevoelige duinecosystemen sterke vergrassing op en verdwijnt de karakteristieke duinvegetatie. De stikstofdepositie in Nederland wordt sinds de jaren negentig berekend met het rekenmodel OPS. Vanaf 2005 kunnen deze berekeningen vergeleken worden met ammoniakmetingen van het 'Meetnet Ammoniak in Natuurgebieden' (MAN). De waarschijnlijke oorzaak voor het verschil tussen berekeningen en metingen is dat de emissie van ammoniak vanuit de kustzone naar de atmosfeer niet in het OPS-model is meegenomen. Door een emissiebronterm voor ammoniak uit zee aan het model toe te voegen, op basis van het gemiddelde algenpatroon in de Noordzee en Waddenzee, verbetert de 'match' tussen de concentratieberekeningen door het model en de gemeten ammoniakconcentraties in duingebieden. De extra emissiebron voor OPS is berekend op basis van het ruimtelijke patroon dat de algen in de Noordzee en de Waddenzee vertonen. Algen lijken een goede indicator te zijn voor de hoeveelheid ammoniak die vrijkomt naar de lucht in de kustzone. Ammoniakconcentraties in duingebieden zijn vervolgens met deze extra emissieterm berekend. Door deze werkwijze is de concentratieberekening op de MAN-meetpunten sterk verbeterd. Omdat er nog geen volledige causale onderbouwing van het proces beschikbaar is, is ook niet met zekerheid te zeggen of deze resultaten in de toekomst blijven gelden. Om de procesmatige onderbouwing van de ammoniakstroom uit zee naar de duinen te verbeteren, zijn nader onderzoek en meer data nodig. Daarnaast zijn de nu beschikbare meetgegevens (nog) ontoereikend om de Zeeuwse en Zuid-Hollandse wateren in deze studie te kunnen betrekken, evenals de situatie rond het IJsselmeer. De veel te lage modelwaarden voor deze locaties kunnen daardoor nog niet worden verbeterd. Om dit op termijn toch te kunnen afleiden is een voorlopige voortzetting van de (tijdelijke) metingen voor deze genoemde locaties nodig. Dit zou meegenomen kunnen worden in de afspraken die gemaakt moeten worden tussen het ministerie van Economische Zaken en het RIVM over de stikstofmonitoring, met name het MAN.Nitrogen compounds are being emitted in large amounts in The Netherlands, causing nitrogen deposition to be the most important problem for Dutch nature at this moment. Measured ammonia concentrations in the nature reserves along the coast are systematically higher than in model calculations ('dune gap'). The main cause of this discrepancy between calculations and measurements was probably the lack of an inventory for ammonia emitted out of the coastal sea zone into the atmosphere. The nitrogen deposition in The Netherlands is being calculated with the mathematical model OPS and is compared with ammonia measurements of the 'Monitoring network Ammonia in Nature reserves' (in Dutch: MAN). The addition of an emission source for ammonia from the sea in the OPS model, based on the average chlorophyll-a (algae) concentrations in the North Sea and the Wadden Sea, results in a largely improved match between the modeled and measured concentrations of ammonia in the coastal zone. Since a full physical/biological description of the process is not yet available, it cannot be concluded that the same results will hold for future scenarios. Such a process-based description of the ammonia flow from the sea to the dunes requires further research and data collection. It is, however, uncertain whether enough knowledge about these processes will become available to provide for a detailed process-based description of ammonia emissions in coastal areas. The situation around the 'Zeeuwse en Zuid-Hollandse Wateren', where the ammonia concentrations measured are also up to several times higher when compared to model calculations, is not included in this report, as during this study too few measurements were available. The same holds for the situation around the IJsselmeer.Ministerie van E