| 1. |
- Butler, Peter, et al.
(författare)
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Coulomb excitation of pear-shaped nuclei
- 2019
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Ingår i: - : EDP Sciences. ; , s. 01007-01007
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Konferensbidrag (refereegranskat)abstract
- There is a large body of evidence that atomic nuclei can undergo octupole distortion and assume the shape of a pear. This phenomenon is important for measurements of electric-dipole moments of atoms, which would indicate CP violation and hence probe physics beyond the Standard Model of particle physics. Isotopes of both radon and radium have been identified as candidates for such measurements. Here, we have observed the low-lying quantum states in 224Rn and 226Rn by accelerating beams of these radioactive nuclei. We show that radon isotopes undergo octupole vibrations but do not possess static pear-shapes in their ground states. We conclude that radon atoms provide less favourable conditions for the enhancement of a measurable atomic electric-dipole moment.
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| 2. |
- Boas, Ingrid, et al.
(författare)
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Climate Migration Myths
- 2019
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Ingår i: Nature Climate Change. - : Nature Publishing Group. - 1758-678X .- 1758-6798. ; 9:12, s. 901-903
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Tidskriftsartikel (refereegranskat)abstract
- Misleading claims about mass migration induced by climate change continue to surface in both academia and policy. This requires a new research agenda on ‘climate mobilities’ that moves beyond simplistic assumptions and more accurately advances knowledge of the nexus between human mobility and climate change.
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| 3. |
- Debnath, Shubhranshu, et al.
(författare)
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Lentiviral Vectors with Cellular Promoters Correct Anemia and Lethal Bone Marrow Failure in a Mouse Model for Diamond-Blackfan Anemia
- 2017
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Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0016. ; 25:8, s. 1805-1814
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Tidskriftsartikel (refereegranskat)abstract
- Diamond-Blackfan anemia is a congenital erythroid hypoplasia and is associated with physical malformations and a predisposition to cancer. Twenty-five percent of patients with Diamond-Blackfan anemia have mutations in a gene encoding ribosomal protein S19 (RPS19). Through overexpression of RPS19 using a lentiviral vector with the spleen focus-forming virus promoter, we demonstrated that the Diamond-Blackfan anemia phenotype can be successfully treated in Rps19-deficient mice. In our present study, we assessed the efficacy of a clinically relevant promoter, the human elongation factor 1α short promoter, with or without the locus control region of the β-globin gene for treatment of RPS19-deficient Diamond-Blackfan anemia. The findings demonstrate that these vectors rescue the proliferation defect and improve erythroid development of transduced RPS19-deficient bone marrow cells. Remarkably, bone marrow failure and severe anemia in Rps19-deficient mice was cured with enforced expression of RPS19 driven by the elongation factor 1α short promoter. We also demonstrate that RPS19-deficient bone marrow cells can be transduced and these cells have the capacity to repopulate bone marrow in long-term reconstituted mice. Our results collectively demonstrate the feasibility to cure RPS19-deficient Diamond-Blackfan anemia using lentiviral vectors with cellular promoters that possess a reduced risk of insertional mutagenesis. Diamond-Blackfan anemia is a congenital erythroid hypoplasia. Twenty-five percent of patients have mutations in a gene encoding ribosomal protein S19. Using an RPS19-deficient mouse model, Debnath et al. demonstrate the feasibility to cure RPS19-deficient Diamond-Blackfan anemia by means of lentiviral vectors with cellular promoters that possess a reduced risk of insertional mutagenesis.
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| 4. |
- Hamer, Davidson H., et al.
(författare)
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Travel-Associated Zika Virus Disease Acquired in the Americas Through February 2016 A GeoSentinel Analysis
- 2017
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Ingår i: Annals of Internal Medicine. - Philadelphia : American College of Physicians. - 0003-4819 .- 1539-3704. ; 166:2, s. 99-108
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Tidskriftsartikel (refereegranskat)abstract
- Background: Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. Objective: To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. Design: Descriptive, using GeoSentinel records. Setting: 63 travel and tropical medicine clinics in 30 countries. Patients: Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016. Measurements: Frequencies of demographic, trip, and clinical characteristics and complications. Results: Starting in May 2015, 93 cases of Zika virus disease were reported. Common symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine percent of patients were exposed in South America; 71% were diagnosed in Europe. Case status was established most commonly by polymerase chain reaction (PCR) testing of blood and less often by PCR testing of other body fluids or serology and plaque-reduction neutralization testing. Two patients developed Guillain-Barre syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major fetal neurologic abnormalities, and intrauterine fetal death). Limitation: Surveillance data collected by specialized clinics may not be representative of all ill returned travelers, and denominator data are unavailable. Conclusion: These surveillance data help characterize the clinical manifestations and adverse outcomes of Zika virus disease among travelers infected in the Americas and show a need for global standardization of diagnostic testing. The serious fetal complications observed in this study highlight the importance of travel advisories and prevention measures for pregnant women and their partners. Travelers are sentinels for global Zika virus circulation and may facilitate further transmission.
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| 5. |
- Löfvall, Henrik, et al.
(författare)
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Hematopoietic stem cell-targeted neonatal gene therapy with a clinically applicable lentiviral vector corrects osteopetrosis in oc/oc Mice
- 2019
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Ingår i: Human Gene Therapy. - : Mary Ann Liebert Inc. - 1043-0342 .- 1557-7422. ; 30:11, s. 1395-1404
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Tidskriftsartikel (refereegranskat)abstract
- Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by nonfunctional osteoclasts. Approximately 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. Gene therapy represents a potential alternative treatment to allogeneic stem cell transplantation for IMO. The oc/oc mouse is a model of IMO characterized by a 1,500 bp deletion in the TCIRG1 gene, severe osteopetrosis, and a life span of only 3 weeks. Here we show that the osteopetrotic phenotype in oc/oc mice can be reversed by hematopoietic stem cell-targeted gene therapy with a clinically applicable lentiviral vector expressing a wild-type form of human TCIRG1 under the mammalian promoter elongation factor 1α short (EFS-hT). oc/oc c-kit+ fetal liver cells transduced with EFS-hT were transplanted into sublethally irradiated oc/oc mice by temporal vein injection 1 day after birth. A total of 9 of 12 mice survived long term (19-25 weeks) with evidence of tooth eruption, uncharacteristic of oc/oc mice. Splenocytes were harvested 19-25 weeks after transplantation and differentiated into osteoclasts on bone slices to assess resorption and on plastic to assess TCIRG1 protein expression. Vector-corrected osteoclasts showed human TCIRG1 expression by Western blot. CTX-I release relative to that mediated by oc/oc-derived osteoclasts increased 8-239-fold. Resorption pits on bone slices were observed for osteoclasts derived from 7/9 surviving transplanted oc/oc mice. Histopathology of the bones of surviving animals showed varying degrees of rescued phenotype, the majority with almost full correction. The average vector copy number per cell in the bone marrow was 1.8 ± 0.5. Overall, 75% of transplanted mice exhibited long-term survival and marked reversal of the osteopetrotic bone phenotype. These findings represent a significant step toward the clinical application of gene therapy for IMO.
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| 6. |
- Moscatelli, Ilana, et al.
(författare)
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Targeting NSG Mice Engrafting Cells with a Clinically Applicable Lentiviral Vector Corrects Osteoclasts in Infantile Malignant Osteopetrosis
- 2018
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Ingår i: Human Gene Therapy. - : Mary Ann Liebert Inc. - 1043-0342 .- 1557-7422. ; 29:8, s. 938-949
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Tidskriftsartikel (refereegranskat)abstract
- Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by nonfunctional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to develop a clinically applicable lentiviral vector expressing TCIRG1 to correct osteoclast function in IMO. Two mammalian promoters were compared: elongation factor 1α short (EFS) promoter and chimeric myeloid promoter (ChimP). EFS promoter was chosen for continued experiments, as it performed better. IMO osteoclasts corrected in vitro by a TCIRG1-expressing lentiviral vector driven by EFS (EFS-T) restored Ca2+ release to 92% and the levels of the bone degradation product CTX-I to 95% in the media compared to control osteoclasts. IMO CD34+ cells from five patients transduced with EFS-T were transplanted into NSG mice. Bone marrow was harvested 9–19 weeks after transplantation, and human CD34+ cells were selected, expanded, and seeded on bone slices. Vector-corrected IMO osteoclasts had completely restored Ca2+ release. CTX-I levels in the media were 33% compared to normal osteoclasts. Thus, in summary, evidence is provided that transduction of IMO CD34+ cells with the clinically applicable EFS-T vector leads to full rescue of osteoclasts in vitro and partial rescue of osteoclasts generated from NSG mice engrafting hematopoietic cells. This supports the continued clinical development of gene therapy for IMO.
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