| 1. |
- McGinn, Steven, et al.
(författare)
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New Technologies for DNA analysis-A review of the READNA Project.
- 2016
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Ingår i: New Biotechnology. - : Elsevier BV. - 1876-4347 .- 1871-6784.
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Forskningsöversikt (refereegranskat)abstract
- The REvolutionary Approaches and Devices for Nucleic Acid analysis (READNA) project received funding from the European Commission for 4 1/2 years. The objectives of the project revolved around technological developments in nucleic acid analysis. The project partners have discovered, created and developed a huge body of insights into nucleic acid analysis, ranging from improvements and implementation of current technologies to the most promising sequencing technologies that constitute a 3(rd) and 4(th) generation of sequencing methods with nanopores and in situ sequencing, respectively.
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| 2. |
- Sepehri, Sobhan, 1986, et al.
(författare)
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Homogeneous Differential Magnetic Assay
- 2019
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Ingår i: Acs Sensors. - : American Chemical Society (ACS). - 2379-3694. ; 4:9, s. 2381-2388
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Tidskriftsartikel (refereegranskat)abstract
- Assays are widely used for detection of various targets, including pathogens, drugs, and toxins. Homogeneous assays are promising for the realization of point-of-care diagnostics as they do not require separation, immobilization, or washing steps. For low concentrations of target molecules, the speed and sensitivity of homogeneous assays have hitherto been limited by slow binding kinetics, time-consuming amplification steps, and the presence of a high background signal. Here, we present a homogeneous differential magnetic assay that utilizes a differential magnetic readout that eliminates previous limitations of homogeneous assays. The assay uses a gradiometer sensor configuration combined with precise microfluidic sample handling. This enables simultaneous differential measurement sample containing a synthesized Vibrio cholerae target and a negative control sample, which reduces the background signal and increases the readout speed. Very low concentrations of targets down to femtomolar levels are thus detectable without any additional amplification of the number of targets. Our homogeneous differential magnetic assay method opens new possibilities for rapid and highly sensitive diagnostics at the point of care.
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| 3. |
- Clausson, Carl-Magnus, 1985-, et al.
(författare)
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Compaction of rolling circle amplification products increases signal integrity and signal–to–noise ratio
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 12317:1-10
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Tidskriftsartikel (refereegranskat)abstract
- Rolling circle amplification (RCA) for generation of distinct fluorescent signals in situ relies upon the self-collapsing properties of single-stranded DNA in commonly used RCA-based methods. By introducing a cross-hybridizing DNA oligonucleotide during rolling circle amplification, we demonstrate that the fluorophore-labeled RCA products (RCPs) become smaller. The reduced size of RCPs increases the local concentration of fluorophores and as a result, the signal intensity increases together with the signal-to-noise ratio. Furthermore, we have found that RCPs sometimes tend to disintegrate and may be recorded as several RCPs, a trait that is prevented with our cross-hybridizing DNA oligonucleotide. These effects generated by compaction of RCPs improve accuracy of visual as well as automated in situ analysis for RCA based methods, such as proximity ligation assays (PLA) and padlock probes.
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| 4. |
- Skedung, Lisa, et al.
(författare)
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Feeling small : Exploring the Tactile Perception Limits
- 2013
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 3, s. 2617-
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Tidskriftsartikel (refereegranskat)abstract
- The human finger is exquisitely sensitive in perceiving different materials, but the question remains as to what length scales are capable of being distinguished in active touch. We combine material science with psychophysics to manufacture and haptically explore a series of topographically patterned surfaces of controlled wavelength, but identical chemistry. Strain-induced surface wrinkling and subsequent templating produced 16 surfaces with wrinkle wavelengths ranging from 300 nm to 90 mu m and amplitudes between 7 nm and 4.5 mu m. Perceived similarities of these surfaces (and two blanks) were pairwise scaled by participants, and interdistances among all stimuli were determined by individual differences scaling (INDSCAL). The tactile space thus generated and its two perceptual dimensions were directly linked to surface physical properties - the finger friction coefficient and the wrinkle wavelength. Finally, the lowest amplitude of the wrinkles so distinguished was approximately 10 nm, demonstrating that human tactile discrimination extends to the nanoscale.
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| 5. |
- Arif, Muhammad, et al.
(författare)
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Integrative transcriptomic analysis of tissue-specific metabolic crosstalk after myocardial infarction
- 2021
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Ingår i: Elife. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Myocardial infarction (MI) promotes a range of systemic effects, many of which are unknown. Here, we investigated the alterations associated with MI progression in heart and other metabolically active tissues (liver, skeletal muscle, and adipose) in a mouse model of MI (induced by ligating the left ascending coronary artery) and sham-operated mice. We performed a genomewide transcriptomic analysis on tissue samples obtained 6- and 24 hr post MI or sham operation. By generating tissue-specific biological networks, we observed: (1) dysregulation in multiple biological processes (including immune system, mitochondrial dysfunction, fatty-acid beta-oxidation, and RNA and protein processing) across multiple tissues post MI and (2) tissue-specific dysregulation in biological processes in liver and heart post MI. Finally, we validated our findings in two independent MI cohorts. Overall, our integrative analysis highlighted both common and specific biological responses to MI across a range of metabolically active tissues.
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| 6. |
- Dong, Min, et al.
(författare)
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Botulinum and tetanus neurotoxins
- 2019
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Ingår i: Annual Review of Biochemistry. - : Annual Reviews. - 0066-4154 .- 1545-4509. ; 88, s. 811-837
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Forskningsöversikt (refereegranskat)abstract
- Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the most potent toxins known and cause botulism and tetanus, respectively. BoNTs are also widely utilized as therapeutic toxins. They contain three functional domains responsible for receptor-binding, membrane translocation, and proteolytic cleavage of host proteins required for synaptic vesicle exocytosis. These toxins also have distinct features: BoNTs exist within a progenitor toxin complex (PTC), which protects the toxin and facilitates its absorption in the gastrointestinal tract, whereas TeNT is uniquely transported retrogradely within motor neurons. Our increasing knowledge of these toxins has allowed the development of engineered toxins for medical uses. The discovery of new BoNTs and BoNT-like proteins provides additional tools to understand the evolution of the toxins and to engineer toxin-based therapeutics. This review summarizes the progress on our understanding of BoNTs and TeNT, focusing on the PTC, receptor recognition, new BoNT-like toxins, and therapeutic toxin engineering.
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| 7. |
- Sörensen, Malin H., et al.
(författare)
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Improved enzymatic activity of Thermomyces lanuginosus lipase immobilized in a hydrophobic particulate
- 2010
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier Inc.. - 0021-9797 .- 1095-7103. ; 343:1, s. 359-365
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Tidskriftsartikel (refereegranskat)abstract
- Lipase from Thermomyces lanuginosus has been immobilized within particulate mesoporous silica carriers, with either hydrophilic or hydrophobic supporting surfaces, produced by the newly developed emulsion and solvent evaporation (ESE) method. The Michaelis-Menten model was used to calculate the parameters related to the enzymatic activity of lipase i.e. the turnover number, kcat, and the specific activity. The specific activity was improved by immobilization of lipase onto the hydrophobic support, compared to lipase immobilized onto the hydrophilic support and lipase free in solution. The enhanced enzymatic activity of lipase onto a hydrophobic support was attributed to interfacial activation of the Thermomyces lanuginosus lipase when it is attached to a hydrophobic surface and a reduced denaturation. Confocal scanning laser microscopy (CLSM) studies, of fluorescently tagged lipase, showed that leakage of the lipase from the mesoporous particles was limited to an initial period of only a few hours. Both the rate and the amount of lipase leached were reduced when the lipase was immobilized onto the hydrophobic support.
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| 8. |
- Waligórski, Michael P R, et al.
(författare)
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Cellular parameters and RBE-LET dependences for modelling heavy-ion radiotherapy.
- 2004
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Ingår i: Radiother Oncol. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 73:Supplement 2, s. S173-175
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Tidskriftsartikel (refereegranskat)abstract
- Sets of four parameters (m, Eo, ~o and •) of the cellular track structure model of Katz have been fitted to recently published dataconcerning human melanoma (AA) and mammalian (V79) cells exposed to a variety of lighter ions and to mixed ion-Co60 and ionionirradiation. We discuss the predictive capability of this model and propose standards in reporting cellular radiobiology data forapplication in modelling heavy ion beam radiotherapy.
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| 9. |
- Lee, Sungmin, et al.
(författare)
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Exploiting Temporal Network Structures of Human Interaction to Effectively Immunize Populations
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5, s. e36439-
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Tidskriftsartikel (refereegranskat)abstract
- Decreasing the number of people who must be vaccinated to immunize a community against an infectious disease could both save resources and decrease outbreak sizes. A key to reaching such a lower threshold of immunization is to find and vaccinate people who, through their behavior, are more likely than average to become infected and to spread the disease further. Fortunately, the very behavior that makes these people important to vaccinate can help us to localize them. Earlier studies have shown that one can use previous contacts to find people that are central in static contact networks. However, real contact patterns are not static. In this paper, we investigate if there is additional information in the temporal contact structure for vaccination protocols to exploit. We answer this affirmative by proposing two immunization methods that exploit temporal correlations and showing that these methods outperform a benchmark static-network protocol in four empirical contact datasets under various epidemic scenarios. Both methods rely only on obtainable, local information, and can be implemented in practice. For the datasets directly related to contact patterns of potential disease spreading ( of sexually-transmitted and nosocomial infections respectively), the most efficient protocol is to sample people at random and vaccinate their latest contacts. The network datasets are temporal, which enables us to make more realistic evaluations than earlier studies-we use only information about the past for the purpose of vaccination, and about the future to simulate disease outbreaks. Using analytically tractable models, we identify two temporal structures that explain how the protocols earn their efficiency in the empirical data. This paper is a first step towards real vaccination protocols that exploit temporal-network structure-future work is needed both to characterize the structure of real contact sequences and to devise immunization methods that exploit these.
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| 10. |
- Dahl, Leo, 1995-, et al.
(författare)
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Multiplexed selectivity screening of anti-GPCR antibodies
- 2023
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 9:18
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Tidskriftsartikel (refereegranskat)abstract
- G protein-coupled receptors (GPCRs) control critical cellular signaling pathways. Therapeutic agents including anti-GPCR antibodies (Abs) are being developed to modulate GPCR function. However, validating the selectivity of anti-GPCR Abs is challenging because of sequence similarities among individual receptors within GPCR sub-families. To address this challenge, we developed a multiplexed immunoassay to test >400 anti-GPCR Abs from the Human Protein Atlas targeting a customized library of 215 expressed and solubilized GPCRs representing all GPCR subfamilies. We found that-61% of Abs tested were selective for their intended target,-11% bound off -target, and-28% did not bind to any GPCR. Antigens of on-target Abs were, on average, significantly longer, more disordered, and less likely to be buried in the interior of the GPCR protein than the other Abs. These results provide important insights into the immunogenicity of GPCR epitopes and form a basis for designing therapeu-tic Abs and for detecting pathological auto-Abs against GPCRs.
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