| 1. |
- Nyberg, Lena, 1979, et al.
(author)
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A single-step competitive binding assay for mapping of single DNA molecules
- 2012
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In: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 417:1, s. 404-408
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Journal article (peer-reviewed)abstract
- Optical mapping of genomic DNA is of relevance for a plethora of applications such as scaffolding for sequencing and detection of structural variations as well as identification cif pathogens like bacteria and viruses. For future clinical applications it is desirable to have a fast and robust mapping method based on as few steps as possible. We here demonstrate a single-step method to obtain a DNA barcode that is directly visualized using nanofluidic devices and fluorescence microscopy. Using a mixture of YOYO-1, a bright DNA dye, and netropsin, a natural antibiotic with very high AT specificity, we obtain a DNA map with a fluorescence intensity profile along the DNA that reflects the underlying sequence. The netropsin binds to AT-tetrads and blocks these binding sites from YOYO-1 binding which results in lower fluorescence intensity from AT-rich regions of the DNA. We thus obtain a DNA barcode that is dark in AT-rich regions and bright in GC-rich regions with kilobasepair resolution. We demonstrate the versatility of the method by obtaining a barcode on DNA from the phage T4 that captures its circular permutation and agrees well with its known sequence.
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| 2. |
- Gräns, Albin, 1979, et al.
(author)
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Aerobic scope fails to explain the detrimental effects on growth resulting from warming and elevated CO2 in Atlantic halibut
- 2014
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In: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 217:5, s. 711-717
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Journal article (peer-reviewed)abstract
- As a consequence of increasing atmospheric CO2, the world's oceans are becoming warmer and more acidic. Whilst the ecological effects of these changes are poorly understood, it has been suggested that fish performance including growth will be reduced mainly as a result of limitations in oxygen transport capacity. Contrary to the predictions given by the oxygen- and capacity-limited thermal tolerance hypothesis, we show that aerobic scope and cardiac performance of Atlantic halibut (Hippoglossus hippoglossus) increase following 14–16 weeks exposure to elevated temperatures and even more so in combination with CO2-acidified seawater. However, the increase does not translate into improved growth, demonstrating that oxygen uptake is not the limiting factor for growth performance at high temperatures. Instead, long-term exposure to CO2-acidified seawater reduces growth at temperatures that are frequently encountered by this species in nature, indicating that elevated atmospheric CO2 levels may have serious implications on fish populations in the future.
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| 3. |
- Gräns, Albin, 1979, et al.
(author)
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Effects of acute temperature changes on gut physiology in two species of sculpin from the west coast of Greenland
- 2013
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In: Polar Biology. - : Springer Science and Business Media LLC. - 0722-4060 .- 1432-2056. ; 36:6, s. 775-785
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Journal article (peer-reviewed)abstract
- For a fish to thrive, the gut must function efficiently. This is achieved through a range of processes, including controlled patterns of gut motility and modifications in gut blood flow. The knowledge of how gut functions in fish are affected by environmental temperature is sparse, and in order to understand how changes in climate may affect fish populations, we need to understand how gut blood flow and gut motility are affected by changes in temperature. By simultaneous recording of gut blood flow, gut motility, cardiac output, heart rate and cardiac stroke volume, in vivo at 4, 9 and 14 °C, the acute thermal sensitivity of a thermal generalist (shorthorn sculpin Myoxocephalu scorpius) was compared to the more strictly Arctic species (Arctic sculpin M. scorpioides). Temperature effects on gut motility were further explored in vitro, using isolated smooth muscles. Elevated water temperatures increased gut blood flow and contractile activity. Contraction frequency increased nearly threefold and gut blood flow almost doubled with the 10 °C increase. Both cardiac output and heart rate increased with temperature, while cardiac stroke volume decreased. The cholinergic agonist carbachol was most potent on smooth muscles at 9 °C. There were no differences between the two species, suggesting that the gastrointestinal and cardiovascular systems of Arctic sculpin, although a more pronounced Arctic species, have similar abilities to cope with acute fluctuations in water temperature as shorthorn sculpin. The impact of increased gut activity at higher temperatures needs further investigation before the effects of climate change can be predicted.
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| 4. |
- Hassellöv, Ida-Maja, 1974, et al.
(author)
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Miljörisker sjunkna vrak
- 2014
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Reports (other academic/artistic)abstract
- Arbetet med en nationell strategi för hantering av miljöfarliga vrak påbörjades 2007 med Statskontorets utredning Vrak och ägarlösa båtar, men ingen enskild myndighet har tilldelats övergripande ansvar för vrakfrågan. Utöver ansvarsfrågan har också förväntade höga kostnader för inspektion och sanering av vrak fördröjt det fortsatta arbetet. Ett steg närmare en nationell strategi redovisas här genom regeringsuppdraget Miljörisker sjunkna vrak. Genom samordning och ökat informationsutbyte mellan berörda myndigheter finns stor potential att minska de förväntade kostnaderna för inspektion av vrak och omgivande miljö. Om den föreslagna strategin antas, beräknas informationsläget avseende vraken att snabbt förbättras så att det år 2030 inte längre finns några potentiellt miljöfarliga vrak i svenska vatten.Havs- och vattenmyndigheten (HaV) och Naturvårdsverket har idag delat ansvar för övervakning och åtgärdande av miljögifter i marin miljö. Mot denna bakgrund hade det varit naturligt att låta HaV få ett övergripande ansvar för hantering av miljöfarliga vrak. Genom flexibelt upplägg avseende tidsramar bedöms övervakning och inspektion av potentiellt miljöfarliga vrak kunna utföras genom att HaV ger de berörda myndigheterna uppdrag; kartering och sjömätning (Sjöfartsverket), ROV och dykinspektion (Kustbevakningen och/eller Försvarsmakten), sediment- och bottenförhållanden (Statens geologiska undersökning). En förutsättning är dock väl fungerande samverkan och kommunikation mellan berörda myndigheter. Existerande plattformar för detta finns redan på såväl operativ nivå i form av Projekt ”Sjöstjärnan” - samordning och samverkan mellan myndigheter avseende information och inhämtning av djup- och bottendata; respektive högsta ledningsnivå i form av Samordningsgruppen för havs- och vattenmiljöfrågor (SamHav).Enligt Sjöfartsverkets tidigare inventering (Miljörisker från fartygsvrak, 2011) finns det utmed Sveriges kust knappt tre tusen vrak som inte kan avskrivas utan vidare informationsinhämtning. Drygt trehundra av dessa klassades som potentiellt miljöfarliga. Av dessa har 31 listats som de sannolikt mest miljöfarliga vraken. Listan över de 31 vraken har därför varit utgångspunkt för projektet Miljörisker sjunkna vrak, vars syfte var att ta fram en metod för prioritering och inspektion av potentiellt miljöfarliga vrak.Undervattensinspektion av vrak är kostsamt och kostnaden ökar kraftigt om vrakets läge är otillgängligt. Av de 31 vraken valdes därför nio relativt lättillgängliga vrak ut för noggrannare arkivstudier, samt sjömätning. Utifrån informationen från arkivstudierna och sjömätningen gjordes ett ytterligare urval om fyra vrak (Altnes, Skytteren, Thetis och Villon), vilka även inspekterades med ROV och/eller dykare. Huvudsyftet var att, inför och under arbetet med inspektionerna, utarbeta Standard Operating Procedures (SOPs) som framgent kan användas som stöd inför kommande operationer rörande potentiellt miljöfarliga vrak.Under arbetet med inspektionerna observerades inte några pågående läckage av olja från vraken. Trots denna positiva information är det viktigt att komma ihåg att endast bevis på tomma tankar kan fullt ut avskriva vraken från listan över potentiellt miljöfarliga vrak. Även om det under projektets fältarbete inte observerades läckage av olja, finns dokumenterade läckage sedan tidigare (senast 2008-04-26) för Skytteren. Noterbart är också att Kustbevakningen 2014-06-29, fick rycka ut för att omhänderta olja som börjat läcka efter vraket Immen, norr om Gotska Sandön. Immen var inte med bland fallstudieobjekten i projektet.I tillägg till undervattensinspektion placerades strömmätningsutrustning ut vid vraken Skytteren och Villon. Strömdata kan sedan användas för att modellera ett hypotetiskt spill av olja från ett vrak och ge en indikation på var läckage av olja kan tänkas påverka den marina miljön negativt. Exempel på sådana negativa effekter kan vara försämrad förmåga hos sedimentlevande organismer att omsätta näringsämnen, vilket i sin tur kan påverka hela det marina ekosystemet. Strömdata är också ett viktigt underlag för utformning av övervakningsprogram, exempelvis med passiva provtagare för att detektera läckage av miljöfarlig substans från vrak.Samtlig insamlad data kommer att användas för att validera riskbedömningsverktyget VRAKA, som möjliggör resurseffektiv prioritering av vilka vrak som bör undersökas och/eller saneras. VRAKA, SOPs för inspektion, samt tillgång till specifik kompetens för utvärdering av samtliga resultat är nyckelelement för att kunna presentera en tillförlitlig riskbedömning av potentiellt miljöfarliga vrak. Havs- och vattenmyndigheten skulle kunna vara lämplig myndighet med huvudansvar för miljöfarliga vrak, i operativ samverkan med övriga berörda myndigheter.
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| 5. |
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| 6. |
- Hassellöv, Ida-Maja, 1974, et al.
(author)
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Miljörisker sjunkna vrak II. Undersökningsmetoder och miljöaspekter
- 2015
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Reports (other academic/artistic)abstract
- During 2015 the Swedish Maritime Administration continued the second phase of thegovernmental task Environmental risks from sunken wrecks which first report was finalized2014-10-31 (Dnr: 1399-14-01942-6).The main conclusions from the 2014 report remain; for future handling of potentially pollutingshipwrecks it is recommended that the Swedish Agency for Water and Marine Management isgiven a coordinating responsibility in close cooperation with other competent nationalauthorities, such as Swedish Maritime Administration, Swedish Coastguard, Swedish NationalMaritime Museums, the Geological Survey of Sweden, SMHI, Swedish EPA, and SwedishCivil Contingencies Agency. Through coordination of wreck related operations and activitieswithin the concerned competent authorities’ ordinary areas of responsibility, resourceefficiency is improved. The estimated extra cost for implementation of a national strategy forhandling of the wrecks are estimated to be 10-15 MSEK which should be allocated to thecompetent authorities by the Swedish Agency for Water and Marine Management.The conclusions from 2014 was reinforced during 2015, e.g. through the validation of the riskassessment model VRAKA, which is now available in a first operative version. Additionalecotoxicological experiments on the development of tolerance against PAHs in meiofauna andmicroorganism communities were conducted in a field study in Brofjorden. The mainconclusions from this work is that comprehensive analyzes of PAHs should include alkylatedPAHs, and that exposure to PAHs over time can lead to tolerance development in ammoniumoxidizing bacteria, at the expense of their ability to perform the essential ecosystem servicenitrification.Continued measurements of the bottom currents were made at the wrecks Villon and Skytteren,and at the dumping area west of Måseskär. Measurement series yielded important informationon how measuring equipment at the wreck can be deployed in an optimized way in futuremonitoring program; to calculate the possible spreading of pollution from a wreck, currentmeasurements should be performed upstream from the wreck site, while sensors for thedetection of, for example, oil should be put into the turbulence downstream of the wreck.The current measurement instruments (RDCP) deployed at the Måseskär dump site was trawledup after only three weeks of measurements, but still gave valuable information on the extensivebottom trawling that resuspend (stir up) sediments. Earlier geochemical surveys have shownsignificantly elevated arsenic concentrations in the area and sediment resuspension greatlyincreased the risk for spread of any contaminants in the area. Trawling is not prohibited in thearea, and the current lack of knowledge regarding potential effects on human health whenconsuming seafood from dump areas calls for reflection upon the suitability of trawling in thearea.In addition to the current measurements Swedish Maritime Administration and the SwedishNavy conducted hydrographic survey with multibeam and side scan sonar and ROVinvestigation of the wrecks in the dumping area at Måseskär. 28 wrecks were found, and ROVinvestigation showed cargo holds with dumped torpedoes or mines and other containers in some SjöfartsverketDnr: 1399-14-01942-156of the wrecks. There is some discrepancy between the previously measured elevated arsenicconcentrations in the Måseskär area and recently presented data from historical archives thatdoes not support the theory that chemical weapons were dumped in the area. However, there isa very good correlation between the dominant current direction in the area, and the highestmeasured arsenic concentrations in the area downstream of the wrecks, suggesting some formof arsenic source in the area.
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| 10. |
- Benza, Raymond L., et al.
(author)
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CS1, a controlled-release formulation of valproic acid, for the treatment of patients with pulmonary arterial hypertension: Rationale and design of a Phase 2 clinical trial
- 2024
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In: PULMONARY CIRCULATION. - 2045-8932 .- 2045-8940. ; 14:1
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Journal article (peer-reviewed)abstract
- Although rare, pulmonary arterial hypertension (PAH) is associated with substantial morbidity and a median survival of approximately 7 years, even with treatment. Current medical therapies have a primarily vasodilatory effect and do not modify the underlying pathology of the disease. CS1 is a novel oral, controlled-release formulation of valproic acid, which exhibits a multi-targeted mode of action (pulmonary pressure reduction, reversal of vascular remodeling, anti-inflammatory, anti-fibrotic, and anti-thrombotic) and therefore potential for disease modification and right ventricular modeling in patients with PAH. A Phase 1 study conducted in healthy volunteers indicated favorable safety and tolerability, with no increased risk of bleeding and significant reduction of plasminogen activator inhibitor 1. In an ongoing randomized Phase 2 clinical trial, three doses of open-label CS1 administered for 12 weeks is evaluating the use of multiple outcome measures. The primary endpoint is safety and tolerability, as measured by the occurrence of adverse events. Secondary outcome measures include the use of the CardioMEMS (TM) HF System, which provides a noninvasive method of monitoring pulmonary artery pressure, as well as cardiac magnetic resonance imaging and echocardiography. Other outcomes include changes in risk stratification (using the REVEAL 2.0 and REVEAL Lite 2 tools), patient reported outcomes, functional capacity, 6-min walk distance, actigraphy, and biomarkers. The pharmacokinetic profile of CS1 will also be evaluated. Overall, the novel design and unique, extensive clinical phenotyping of participants in this trial will provide ample evidence to inform the design of any future Phase 3 studies with CS1.
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