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1.
  • Adcox, K, et al. (författare)
  • PHENIX detector overview
  • 2003
  • Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 469-479
  • Tidskriftsartikel (refereegranskat)abstract
    • The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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  • Nelson, G., et al. (författare)
  • QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy
  • 2021
  • Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 284:1, s. 56-73
  • Tidskriftsartikel (refereegranskat)abstract
    • A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics.
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3.
  • Adler, SS, et al. (författare)
  • PHENIX on-line systems
  • 2003
  • Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 560-592
  • Tidskriftsartikel (refereegranskat)abstract
    • The PHENIX On-Line system takes signals from the Front End Modules (FEM) on each detector subsystem for the purpose of generating events for physics analysis. Processing of event data begins when the Data Collection Modules (DCM) receive data via fiber-optic links from the FEMs. The DCMs format and zero suppress the data and generate data packets. These packets go to the Event Builders (EvB) that assemble the events in final form. The Level-1 trigger (LVL1) generates a decision for each beam crossing and eliminates uninteresting events. The FEMs carry out all detector processing of the data so that it is delivered to the DCMs using a standard format. The FEMs also provide buffering for LVL1 trigger processing and DCM data collection. This is carried out using an architecture that is pipelined and deadtimeless. All of this is controlled by the Master Timing System (MTS) that distributes the RHIC clocks. A Level-2 trigger (LVL2) gives additional discrimination. A description of the components and operation of the PHENIX On-Line system is given and the solution to a number of electronic infrastructure problems are discussed. (C) 2002 Elsevier Science B.V. All rights reserved.
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4.
  • Birney, Ewan, et al. (författare)
  • Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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  • Kim, S. W., et al. (författare)
  • Evaluations of NOx and highly reactive VOC emission inventories in Texas and their implications for ozone plume simulations during the Texas Air Quality Study 2006
  • 2011
  • Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:22, s. 11361-11386
  • Tidskriftsartikel (refereegranskat)abstract
    • Satellite and aircraft observations made during the 2006 Texas Air Quality Study (TexAQS) detected strong urban, industrial and power plant plumes in Texas. We simulated these plumes using the Weather Research and Forecasting-Chemistry (WRF-Chem) model with input from the US EPA's 2005 National Emission Inventory (NEI-2005), in order to evaluate emissions of nitrogen oxides (NOx = NO + NO2) and volatile organic compounds (VOCs) in the cities of Houston and Dallas-FortWorth. We compared the model results with satellite retrievals of tropospheric nitrogen dioxide (NO2) columns and airborne in-situ observations of several trace gases including NOx and a number of VOCs. The model and satellite NO2 columns agree well for regions with large power plants and for urban areas that are dominated by mobile sources, such as Dallas. How-ever, in Houston, where significant mobile, industrial, and inport marine vessel sources contribute to NOx emissions, the model NO2 columns are approximately 50 %-70 % higher than the satellite columns. Similar conclusions are drawn from comparisons of the model results with the TexAQS 2006 aircraft observations in Dallas and Houston. For Dallas plumes, the model-simulated NO2 showed good agreement with the aircraft observations. In contrast, the model-simulated NO2 is similar to 60 % higher than the aircraft observations in the Houston plumes. Further analysis indicates that the NEI-2005 NOx emissions over the Houston Ship Channel area are overestimated while the urban Houston NOx emissions are reasonably represented. The comparisons of model and aircraft observations confirm that highly reactive VOC emissions originating from industrial sources in Houston are underestimated in NEI-2005. The update of VOC emissions based on Solar Occultation Flux measurements during the field campaign leads to improved model simulations of ethylene, propylene, and formaldehyde. Reducing NOx emissions in the Houston Ship Channel and increasing highly reactive VOC emissions from the point sources in Houston improve the model's capability of simulating ozone (O-3) plumes observed by the NOAA WP-3D aircraft, although the deficiencies in the model O-3 simulations indicate that many challenges remain for a full understanding of the O-3 formation mechanisms in Houston.
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  • De Gouw, J. A., et al. (författare)
  • Airborne Measurements of Ethene from Industrial Sources Using Laser Photo-Acoustic Spectroscopy
  • 2009
  • Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 43:7, s. 2437-2442
  • Tidskriftsartikel (refereegranskat)abstract
    • A laser photoacoustic spectroscopy (LPAS) instrument was developed and used for aircraft measurements of ethene from industrial sources near Houston, Texas. The instrument provided 20 s measurements with a detection limit of less than 0.7 ppbv. Data from this instrument and from the GC-FID analysis of air samples collected in flight agreed within 15% on average. Ethene fluxes from the Mt. Belvieu chemical complex to the northeast of Houston were quantified during 10 different flights. The average flux was 520 +/- 140 kg h(-1) in agreement with independent results from solar occultation flux (SOF) measurements, and roughly an order of magnitude higher than regulatory emission inventories indicate. This study shows that ethene emissions are routinely at levels that qualify as emission upsets, which need to be reported to regional air quality managers.
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  • Dong, Yiran, et al. (författare)
  • Physiology, Metabolism, and Fossilization of Hot-Spring Filamentous Microbial Mats
  • 2019
  • Ingår i: Astrobiology. - : MARY ANN LIEBERT, INC. - 1531-1074 .- 1557-8070. ; 19:12
  • Tidskriftsartikel (refereegranskat)abstract
    • The evolutionarily ancient Aquificales bacterium Sulfurihydrogenibium spp. dominates filamentous microbial mat communities in shallow, fast-flowing, and dysoxic hot-spring drainage systems around the world. In the present study, field observations of these fettuccini-like microbial mats at Mammoth Hot Springs in Yellowstone National Park are integrated with geology, geochemistry, hydrology, microscopy, and multi-omic molecular biology analyses. Strategic sampling of living filamentous mats along with the hot-spring CaCO3 (travertine) in which they are actively being entombed and fossilized has permitted the first direct linkage of Sulfurihydrogenibium spp. physiology and metabolism with the formation of distinct travertine streamer microbial biomarkers. Results indicate that, during chemoautotrophy and CO2 carbon fixation, the 87-98% Sulfurihydrogenibium-dominated mats utilize chaperons to facilitate enzyme stability and function. High-abundance transcripts and proteins for type IV pili and extracellular polymeric substances (EPSs) are consistent with their strong mucus-rich filaments tens of centimeters long that withstand hydrodynamic shear as they become encrusted by more than 5mm of travertine per day. Their primary energy source is the oxidation of reduced sulfur (e.g., sulfide, sulfur, or thiosulfate) and the simultaneous uptake of extremely low concentrations of dissolved O-2 facilitated by bd-type cytochromes. The formation of elevated travertine ridges permits the Sulfurihydrogenibium-dominated mats to create a shallow platform from which to access low levels of dissolved oxygen at the virtual exclusion of other microorganisms. These ridged travertine streamer microbial biomarkers are well preserved and create a robust fossil record of microbial physiological and metabolic activities in modern and ancient hot-spring ecosystems.
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  • Kaucka, Marketa, et al. (författare)
  • Oriented clonal cell dynamics enables accurate growth and shaping of vertebrate cartilage
  • 2017
  • Ingår i: eLIFE. - : Elife Sciences Publications LTD. - 2050-084X. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Cartilaginous structures are at the core of embryo growth and shaping before the bone forms. Here we report a novel principle of vertebrate cartilage growth that is based on introducing transversally-oriented clones into pre-existing cartilage. This mechanism of growth uncouples the lateral expansion of curved cartilaginous sheets from the control of cartilage thickness, a process which might be the evolutionary mechanism underlying adaptations of facial shape. In rod-shaped cartilage structures (Meckel, ribs and skeletal elements in developing limbs), the transverse integration of clonal columns determines the well-defined diameter and resulting rod-like morphology. We were able to alter cartilage shape by experimentally manipulating clonal geometries. Using in silico modeling, we discovered that anisotropic proliferation might explain cartilage bending and groove formation at the macro-scale.
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  • Newton, P. T., et al. (författare)
  • A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate
  • 2019
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 567:7747
  • Tidskriftsartikel (refereegranskat)abstract
    • Longitudinal bone growth in children is sustained by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification(1). However, it remains unknown how this supply is maintained throughout childhood growth. Chondroprogenitors in the resting zone are thought to be gradually consumed as they supply cells for longitudinal growth(1,2), but this model has never been proved. Here, using clonal genetic tracing with multicolour reporters and functional perturbations, we demonstrate that longitudinal growth during the fetal and neonatal periods involves depletion of chondroprogenitors, whereas later in life, coinciding with the formation of the secondary ossification centre, chondroprogenitors acquire the capacity for self-renewal, resulting in the formation of large, stable monoclonal columns of chondrocytes. Simultaneously, chondroprogenitors begin to express stem cell markers and undergo symmetric cell division. Regulation of the pool of self-renewing progenitors involves the hedgehog and mammalian target of rapamycin complex 1 (mTORC1) signalling pathways. Our findings indicate that a stem cell niche develops postnatally in the epiphyseal growth plate, which provides a continuous supply of chondrocytes over a prolonged period.
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  • Parrish, D. D., et al. (författare)
  • Primary and secondary sources of formaldehyde in urban atmospheres: Houston Texas region
  • 2012
  • Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:7, s. 3273-3288
  • Tidskriftsartikel (refereegranskat)abstract
    • We evaluate the rates of secondary production and primary emission of formaldehyde (CH2O) from petrochemical industrial facilities and on-road vehicles in the Houston Texas region. This evaluation is based upon ambient measurements collected during field studies in 2000, 2006 and 2009. The predominant CH2O source (92 +/- 4% of total) is secondary production formed during the atmospheric oxidation of highly reactive volatile organic compounds (HRVOCs) emitted from the petrochemical facilities. Smaller contributions are primary emissions from these facilities (4 +/- 2%), and secondary production (similar to 3%) and primary emissions (similar to 1%) from vehicles. The primary emissions from both sectors are well quantified by current emission inventories. Since secondary production dominates, control efforts directed at primary CH2O emissions cannot address the large majority of CH2O sources in the Houston area, although there may still be a role for such efforts. Ongoing efforts to control alkene emissions from the petrochemical facilities, as well as volatile organic compound emissions from the motor vehicle fleet, will effectively reduce the CH2O concentrations in the Houston region. We do not address other emission sectors, such as off-road mobile sources or secondary formation from biogenic hydrocarbons. Previous analyses based on correlations between ambient concentrations of CH2O and various marker species have suggested much larger primary emissions of CH2O, but those results neglect confounding effects of dilution and loss processes, and do not demonstrate the causes of the observed correlations. Similar problems must be suspected in any source apportionment analysis of secondary species based upon correlations of ambient concentrations of pollutants.
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  • Brown, H, et al. (författare)
  • Synaptotagmin III isoform is compartmentalized in pancreatic beta-cells and has a functional role in exocytosis
  • 2000
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 49:3, s. 383-391
  • Tidskriftsartikel (refereegranskat)abstract
    • Synaptotagmin is involved in Ca2+-regulated secretion and has been suggested to serve as a general Ca2+ sensor on the membrane of secretory vesicles in neuronal cells. Insulin exocytosis from the pancreatic beta-cell is an example of a Ca2+-dependent secretory process. Previous studies of pancreatic beta-cells were unable to show presence of synaptotagmin I. We now present biochemical and immunohistochemical data showing that synaptotagmin III is present in pancreatic beta-cells as well as in the insulin-secreting cell line HIT-T15 and in rat insulinoma. By subcellular fractionation, we found synaptotagmin III in high-density fractions together with insulin and secretogranin I, indicating colocalization of synaptotagmin III and insulin in secretory granules. We could also show that blockade of synaptotagmin III by a specific antibody inhibited Ca2+-induced changes in beta-cell membrane capacitance, suggesting that synaptotagmin III is part of the functional protein complex regulating beta-cell exocytosis. The synaptotagmin III antibody did not affect the activity of the voltage-gated L-type Ca2+-channel. These findings are compatible with the view that synaptotagmin III, because of its distinct localization in the pancreatic beta-cell, functionally modulates insulin exocytosis. This indicates that synaptotagmin may have a general role in the regulation of exocytosis not only in neuronal cells but also in endocrine cells.
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  • Dent, E., et al. (författare)
  • Physical Frailty : ICFSR International Clinical Practice Guidelines for Identification and Management
  • 2019
  • Ingår i: The Journal of Nutrition, Health & Aging. - : SPRINGER FRANCE. - 1279-7707 .- 1760-4788. ; 23:9, s. 771-787
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults.Methods: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care.Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation).Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.
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  • Fried, D., et al. (författare)
  • Complexity of Canadian traveler problem variants
  • 2013
  • Ingår i: Theoretical Computer Science. - : Elsevier BV. - 0304-3975 .- 1879-2294. ; 487, s. 1-16
  • Tidskriftsartikel (refereegranskat)abstract
    • The Canadian traveler problem (CTP) is the problem of traversing a given graph, where some of the edges may be blocked-a state which is revealed only upon reaching an incident vertex. Originally stated by Papadimitriou and Yannakakis (1991) [1], the adversarial version of the CTP was shown to be PSPACE-complete, with the stochastic version shown to be in PSPACE and #P-hard. We show that the stochastic CTP is also PSPACE-complete: initially proving PSPACE-hardness for the dependent version of the stochastic CTP, and proceeding with gadgets that allow us to extend the proof to the independent case. Since for disjoint-path graphs, the CTP can be solved in polynomial time, we examine the complexity of the more general remote-sensing CTP, and show that it is NP-hard even for disjoint-path graphs.
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  • Fried, S, et al. (författare)
  • Outpatients' perspectives on problems and needs related to female genital mutilation/cutting: a qualitative study from somaliland
  • 2013
  • Ingår i: Obstetrics and gynecology international. - : Hindawi Limited. - 1687-9589 .- 1687-9597. ; 2013, s. 165893-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim. To explore female outpatients’ perspectives on problems related to female genital mutilation/cutting (FGM/C) and their views on information, care, and counseling.Setting. An FGM/C support center at a maternity clinic in Hargeisa, Somaliland.Methods. A qualitative, descriptive study, using content analysis of seven semistructured interviews with female outpatients.Results. All participants had been ignorant of the etiology of their FGM/C-related complications and hesitant to seek care. All had undergone infibulation but did not wish the same for their daughters. In recent years they had learnt through religious leaders and media campaigns that infibulation was unapproved by Islam. A less severe FGM/C type, “Sunna,” was more accepted; however, few could define what “Sunna” meant. Condemning and ridiculing attitudes against uncircumcised women prevailed in their community.Conclusions. New ideas and concepts related to FGM/C enter the common discourse in the Somali society while traditional norms and values still prevail. Religion was shown to have a strong impact on FGM/C practices and beliefs. Interventions aiming to raise awareness of health consequences of all types of FGM/C, as well as where to seek care for complications, are needed in Somaliland. Involvement of religious leaders in anti-FGM/C programs is essential.
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  • Isman, E, et al. (författare)
  • Midwives' Experiences in Providing Care and Counselling to Women with Female Genital Mutilation (FGM) Related Problems
  • 2013
  • Ingår i: Obstetrics and gynecology international. - : Hindawi Limited. - 1687-9589 .- 1687-9597. ; 2013, s. 785148-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim. The aim of this study was to elucidate midwives experiences in providing care and counselling to women with FGM related problems.Setting. The study was conducted at a maternity clinic in Hargeisa, Somaliland.Method. A qualitative, inductive study were performed with eight midwives living in Somaliland. The interviews had semi-structured questions. Content analysis was used for the analysis.Findings. The main findings of the present study were how midwives are challenged by culture and religion when providing FGM counselling. The most prominent challenge is the perception that FGM is an important part of the culture and from this point of view the midwives work is apprehended as interfering and subverting the Somali culture. Having personal experience of FGM emerged as a benefit when counselling women.Conclusion. There is a contradiction between the professional actions of performing FGM despite a personal belief against FGM. Midwives as a professional group could be important agents of change and further research is needed about the midwives role in this process.
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  • Kaucka, M., et al. (författare)
  • Altered developmental programs and oriented cell divisions lead to bulky bones during salamander limb regeneration
  • 2022
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • There are major differences in duration and scale at which limb development and regeneration proceed, raising the question to what extent regeneration is a recapitulation of development. We address this by analyzing skeletal elements using a combination of micro-CT imaging, molecular profiling and clonal cell tracing. We find that, in contrast to development, regenerative skeletal growth is accomplished based entirely on cartilage expansion prior to ossification, not limiting the transversal cartilage expansion and resulting in bulkier skeletal parts. The oriented extension of salamander cartilage and bone appear similar to the development of basicranial synchondroses in mammals, as we found no evidence for cartilage stem cell niches or growth plate-like structures during neither development nor regeneration. Both regenerative and developmental ossification in salamanders start from the cortical bone and proceeds inwards, showing the diversity of schemes for the synchrony of cortical and endochondral ossification among vertebrates. Normal limb development relies on synchronized formation of cartilage and bone. Here, the authors show that in salamander limb regeneration these processes are decoupled: ossification occurs after the final size of regenerating cartilage is reached, allowing fast regeneration and leading to bulky bones.
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  • Kaucka, Marketa, et al. (författare)
  • Analysis of neural crest-derived clones reveals novel aspects of facial development
  • 2016
  • Ingår i: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 2:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Cranial neural crest cells populate the future facial region and produce ectomesenchyme-derived tissues, such as cartilage, bone, dermis, smooth muscle, adipocytes, and many others. However, the contribution of individual neural crest cells to certain facial locations and the general spatial clonal organization of the ectomesenchyme have not been determined. We investigated how neural crest cells give rise to clonally organized ectomesenchyme and how this early ectomesenchyme behaves during the developmental processes that shape the face. Using a combination of mouse and zebrafish models, we analyzed individual migration, cell crowd movement, oriented cell division, clonal spatial overlapping, and multilineage differentiation. The early face appears to be built from multiple spatially defined overlapping ectomesenchymal clones. During early face development, these clones remain oligopotent and generate various tissues in a given location. By combining clonal analysis, computer simulations, mouse mutants, and live imaging, we show that facial shaping results from an array of local cellular activities in the ectomesenchyme. These activities mostly involve oriented divisions and crowd movements of cells during morphogenetic events. Cellular behavior that can be recognized as individual cell migration is very limited and short-ranged and likely results from cellular mixing due to the proliferation activity of the tissue. These cellular mechanisms resemble the strategy behind limb bud morphogenesis, suggesting the possibility of common principles and deep homology between facial and limb outgrowth.
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  • Lewander, Magnus, et al. (författare)
  • Fast and sensitive time-multiplexed gas sensing of multiple lines using a miniature telecom diode laser between 1529 nm and 1565 nm
  • 2011
  • Ingår i: Applied Physics B. - : Springer Science and Business Media LLC. - 0946-2171 .- 1432-0649. ; 104:3, s. 715-723
  • Tidskriftsartikel (refereegranskat)abstract
    • High-sensitive multi-species detection around 1550 nm using a modulated grating Y-branch, MG-Y, diode laser tunable between 1529 nm and 1565 nm is presented. The MG-Y diode laser is based on the Vernier effect of two modulated gratings, and exhibits quasi-continuous tuning over 36 nm. Multi-species detection is achieved by fast sequential scanning of single absorption lines of CH4, CO, C2H2, and CO2 distributed over the tuning range of the diode laser. The laser wavelength is scanned about 10 GHz around each absorption line for 5 ms and this is followed by a discrete large jump in operating wavelength to the next line. The MG-Y diode laser has a good repeatability in output frequency between sequential scan segments (< 10 MHz) enabling averaging of the scans. The setup employs digital wavelength modulation spectroscopy, dWMS, with Fourier-based WMS retrieval, applicable through the use of data acquisition cards and coherent sampling. Absorbance sensitivity using 2f-WMS signals of 7x10(-7) in 30 s (all precisions in this paper are at the 1 sigma level) is demonstrated for sensing of four gases and 2x10(-7) when only one gas is detected. Corresponding numbers for 0.5 s of averaging are 4x10(-6) and 1x10(-6).
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  • Nissenbaum, J, et al. (författare)
  • Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2
  • 2010
  • Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 20:9, s. 1180-1190
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic neuropathic pain is affected by specifics of the precipitating neural pathology, psychosocial factors, and by genetic predisposition. Little is known about the identity of predisposing genes. Using an integrative approach, we discovered that CACNG2 significantly affects susceptibility to chronic pain following nerve injury. CACNG2 encodes for stargazin, a protein intimately involved in the trafficking of glutamatergic AMPA receptors. The protein might also be a Ca2+ channel subunit. CACNG2 has previously been implicated in epilepsy. Initially, using two fine-mapping strategies in a mouse model (recombinant progeny testing [RPT] and recombinant inbred segregation test [RIST]), we mapped a pain-related quantitative trait locus (QTL) (Pain1) into a 4.2-Mb interval on chromosome 15. This interval includes 155 genes. Subsequently, bioinformatics and whole-genome microarray expression analysis were used to narrow the list of candidates and ultimately to pinpoint Cacng2 as a likely candidate. Analysis of stargazer mice, a Cacng2 hypomorphic mutant, provided electrophysiological and behavioral evidence for the gene's functional role in pain processing. Finally, we showed that human CACNG2 polymorphisms are associated with chronic pain in a cohort of cancer patients who underwent breast surgery. Our findings provide novel information on the genetic basis of neuropathic pain and new insights into pain physiology that may ultimately enable better treatments.
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  • Persson, AK, et al. (författare)
  • Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain
  • 2009
  • Ingår i: Molecular pain. - : SAGE Publications. - 1744-8069. ; 5, s. 7-
  • Tidskriftsartikel (refereegranskat)abstract
    • Nerve injury-triggered hyperexcitability in primary sensory neurons is considered a major source of chronic neuropathic pain. The hyperexcitability, in turn, is thought to be related to transcriptional switching in afferent cell somata. Analysis using expression microarrays has revealed that many genes are regulated in the dorsal root ganglion (DRG) following axotomy. But which contribute to pain phenotype versus other nerve injury-evoked processes such as nerve regeneration? Using the L5 spinal nerve ligation model of neuropathy we examined differential changes in gene expression in the L5 (and L4) DRGs in five mouse strains with contrasting susceptibility to neuropathic pain. We sought genes for which the degree of regulation correlates with strain-specific pain phenotype. Results In an initial experiment six candidate genes previously identified as important in pain physiology were selected for in situ hybridization to DRG sections. Among these, regulation of the Na+ channel α subunit Scn11a correlated with levels of spontaneous pain behavior, and regulation of the cool receptor Trpm8 correlated with heat hypersensibility. In a larger scale experiment, mRNA extracted from individual mouse DRGs was processed on Affymetrix whole-genome expression microarrays. Overall, 2552 ± 477 transcripts were significantly regulated in the axotomized L5DRG 3 days postoperatively. However, in only a small fraction of these was the degree of regulation correlated with pain behavior across strains. Very few genes in the “uninjured” L4DRG showed altered expression (24 ± 28). Conclusion Correlational analysis based on in situ hybridization provided evidence that differential regulation of Scn11a and Trpm8 contributes to across-strain variability in pain phenotype. This does not, of course, constitute evidence that the others are unrelated to pain. Correlational analysis based on microarray data yielded a larger “look-up table” of genes whose regulation likely contributes to pain variability. While this list is enriched in genes of potential importance for pain physiology, and is relatively free of the bias inherent in the candidate gene approach, additional steps are required to clarify which transcripts on the list are in fact of functional importance.
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  • Shahidi, MK, et al. (författare)
  • Three-dimensional Imaging Reveals New Compartments and Structural Adaptations in Odontoblasts
  • 2015
  • Ingår i: Journal of dental research. - : SAGE Publications. - 1544-0591 .- 0022-0345. ; 94:7, s. 945-954
  • Tidskriftsartikel (refereegranskat)abstract
    • In organized tissues, the precise geometry and the overall shape are critical for the specialized functions that the cells carry out. Odontoblasts are major matrix-producing cells of the tooth and have also been suggested to participate in sensory transmission. However, refined morphologic data on these important cells are limited, which hampers the analysis and understanding of their cellular functions. We took advantage of fluorescent color-coding genetic tracing to visualize and reconstruct in 3 dimensions single odontoblasts, pulp cells, and their assemblages. Our results show distinct structural features and compartments of odontoblasts at different stages of maturation, with regard to overall cellular shape, formation of the main process, orientation, and matrix deposition. We demonstrate previously unanticipated contacts between the processes of pulp cells and odontoblasts. All reported data are related to mouse incisor tooth. We also show that odontoblasts express TRPM5 and Piezo2 ion channels. Piezo2 is expressed ubiquitously, while TRPM5 is asymmetrically distributed with distinct localization to regions proximal to and within odontoblast processes.
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49.
  • Tack, J, et al. (författare)
  • Diagnosis and treatment of chronic constipation--a European perspective.
  • 2011
  • Ingår i: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 23:8, s. 697-710
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: Although constipation can be a chronic and severe problem, it is largely treated empirically. Evidence for the efficacy of some of the older laxatives from well-designed trials is limited. Patients often report high levels of dissatisfaction with their treatment, which is attributed to a lack of efficacy or unpleasant side-effects. Management guidelines and recommendations are limited and are not sufficiently current to include treatments that became available more recently, such as prokinetic agents in Europe. PURPOSE: We present an overview of the pathophysiology, diagnosis, current management and available guidelines for the treatment of chronic constipation, and include recent data on the efficacy and potential clinical use of the more newly available therapeutic agents. Based on published algorithms and guidelines on the management of chronic constipation, secondary pathologies and causes are first excluded and then diet, lifestyle, and, if available, behavioral measures adopted. If these fail, bulk-forming, osmotic, and stimulant laxatives can be used. If symptoms are not satisfactorily resolved, a prokinetic agent such as prucalopride can be prescribed. Biofeedback is recommended as a treatment for chronic constipation in patients with disordered defecation. Surgery should only be considered once all other treatment options have been exhausted.
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