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| 2. |
- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 3. |
- Akkaya, Munir, et al.
(författare)
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A single-nucleotide polymorphism in a Plasmodium berghei ApiAP2 transcription factor alters the development of host immunity
- 2020
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Ingår i: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 6:6
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Tidskriftsartikel (refereegranskat)abstract
- The acquisition of malaria immunity is both remarkably slow and unpredictable. At present, we know little about the malaria parasite genes that influence the host's ability to mount a protective immune response. Here, we show that a single-nucleotide polymorphism (SNP) resulting in a single amino acid change (S to F) in an ApiAP2 transcription factor in the rodent malaria parasite Plasmodium berghei (Pb) NK65 allowed infected mice to mount a T helper cell 1 (T(H)1)-type immune response that controlled subsequent infections. As compared to PbNK65(S), PbNK65(F) parasites differentially expressed 46 genes, most of which are predicted to play roles in immune evasion. PbNK65(F) infections resulted in an early interferon-gamma response and a later expansion of germinal centers, resulting in high levels of infected red blood cell-specific T(H)1-type immunoglobulin G2b (IgG2b) and IgG2c antibodies. Thus, the Pb ApiAP2 transcription factor functions as a critical parasite virulence factor in malaria infections.
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| 4. |
- Akkaya, Munir, et al.
(författare)
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Testing the impact of a single nucleotide polymorphism in a Plasmodium berghei ApiAP2 transcription factor on experimental cerebral malaria in mice
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral malaria (CM) is the deadliest form of severe Plasmodium infections. Currently, we have limited understanding of the mechanisms by which Plasmodium parasites induce CM. The mouse model of CM, experimental CM (ECM), induced by infection with the rodent parasite, Plasmodium berghei ANKA (PbANKA) has been extensively used to study the pathophysiology of CM. Recent genomic analyses revealed that the coding regions of PbANKA and the closely related Plasmodium berghei NK65 (PbNK65), that does not cause ECM, differ in only 21 single nucleotide polymorphysims (SNPs). Thus, the SNP-containing genes might contribute to the pathogenesis of ECM. Although the majority of these SNPs are located in genes of unknown function, one SNP is located in the DNA binding site of a member of the Plasmodium ApiAP2 transcription factor family, that we recently showed functions as a virulence factor alternating the host's immune response to the parasite. Here, we investigated the impact of this SNP on the development of ECM. Our results using CRISPR-Cas9 engineered parasites indicate that despite its immune modulatory function, the SNP is neither necessary nor sufficient to induce ECM and thus cannot account for parasite strain-specific differences in ECM phenotypes.
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| 7. |
- Richards, Cathy E., et al.
(författare)
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Development of a novel weighted ranking method for immunohistochemical quantification of a heterogeneously expressed protein in gastro-esophageal cancers
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- High expression of Junctional Adhesion Molecule-A (JAM-A) has been linked with poor prognosis in several cancers, including breast cancers overexpressing the human epidermal growth factor receptor-2 (HER2). Furthermore, JAM-A expression has been linked with regulating that of HER2, and associated with the development of resistance to HER2-targeted therapies in breast cancer patients. The purpose of this study was to establish a potential relationship between JAM-A and HER2 in HER2-overexpressing gastro-esophageal (GE) cancers. Interrogation of gene expression datasets revealed that high JAM-A mRNA expression was associated with poorer survival in HER2-positive gastric cancer patients. However, high intra-tumoral heterogeneity of JAM-A protein expression was noted upon immunohistochemical scoring of a GE cancer tissue microarray (TMA), precluding a simple confirmation of any relationship between JAM-A and HER2 at protein level. However, in a test-set of 25 full-face GE cancer tissue sections, a novel weighted ranking system proved effective in capturing JAM-A intra-tumoral heterogeneity and confirming statistically sig-nificant correlations between JAM-A/HER2 expression. Given the growing importance of immuno-histochemistry in stratifying cancer patients for the receipt of new targeted therapies, this may sound a cautionary note against over-relying on cancer TMAs in biomarker discovery studies of heterogeneously expressed proteins. It also highlights a timely need to develop validated mechanisms of capturing intra-tumoral heterogeneity to aid in future biomarker/therapeutic target development for the benefit of cancer patients.
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| 8. |
- Tobin, John J., et al.
(författare)
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The VLA/ALMA Nascent Disk and Multiplicity (VANDAM) Survey of Orion Protostars. II. A Statistical Characterization of Class 0 and Class i Protostellar Disks
- 2020
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 890:2
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Tidskriftsartikel (refereegranskat)abstract
- We have conducted a survey of 328 protostars in the Orion molecular clouds with the Atacama Large Millimeter/submillimeter Array at 0.87 mm at a resolution of ∼0.″1 (40 au), including observations with the Very Large Array at 9 mm toward 148 protostars at a resolution of ∼0.″08 (32 au). This is the largest multiwavelength survey of protostars at this resolution by an order of magnitude. We use the dust continuum emission at 0.87 and 9 mm to measure the dust disk radii and masses toward the Class 0, Class I, and flat-spectrum protostars, characterizing the evolution of these disk properties in the protostellar phase. The mean dust disk radii for the Class 0, Class I, and flat-spectrum protostars are 44.9-3.4+5.8, 37.0-3.0+4.9, and 28.5-2.3+3.7 au, respectively, and the mean protostellar dust disk masses are 25.9-4.0+7.7, 14.9-2.2+3.8, 11.6-1.9+3.5 M⊙, respectively. The decrease in dust disk masses is expected from disk evolution and accretion, but the decrease in disk radii may point to the initial conditions of star formation not leading to the systematic growth of disk radii or that radial drift is keeping the dust disk sizes small. At least 146 protostellar disks (35% of 379 detected 0.87 mm continuum sources plus 42 nondetections) have disk radii greater than 50 au in our sample. These properties are not found to vary significantly between different regions within Orion. The protostellar dust disk mass distributions are systematically larger than those of Class II disks by a factor of >4, providing evidence that the cores of giant planets may need to at least begin their formation during the protostellar phase.
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| 9. |
- Wright, Gillian, et al.
(författare)
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The Mid-infrared Instrument for JWST and Its In-flight Performance
- 2023
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Ingår i: Publications of the Astronomical Society of the Pacific. - 0004-6280 .- 1538-3873. ; 135:1046
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Tidskriftsartikel (refereegranskat)abstract
- The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5 μm. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and spectroscopy at resolutions of λ/Δλ ∼ 100-3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI.
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