| 1. |
- Burstein, R., et al.
(författare)
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Mapping 123 million neonatal, infant and child deaths between 2000 and 2017
- 2019
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7778, s. 353-358
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Tidskriftsartikel (refereegranskat)abstract
- Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations. © 2019, The Author(s).
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| 2. |
- Behboudi, A, et al.
(författare)
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Functional significance of absence : The chromosomal segment harboring the Tp53 gene is missing in the T55 rat radiation hybrid mapping panel
- 2002
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Ingår i: Genomics. - : Academic Press. - 0888-7543 .- 1089-8646. ; 79:6, s. 844-848
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Tidskriftsartikel (refereegranskat)abstract
- The T55 rat radiation hybrid (RH) mapping panel has been reported to retain the entire rat genome at retention frequencies between 22% and 37%. However, we found that a small segment of rat chromosome 10 harboring at least four different genes, including Tp53, was completely absent from the panel (retention frequency = 0%). Two other markers located in the vicinity exhibited much reduced retention (2–6%). RH clones are generated by transferring highly fragmented DNA into a recipient cell. There might be a strong selection against the transfer and retention of chromosome segments harboring an intact Tp53, as the action of this gene might prevent proliferation and establishment of the RH clone. Our finding further suggests that unexpected low retention or absence of chromosome segments in an RH panel may represent indications that the segments harbor genes with important functions in cell proliferation control.
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| 3. |
- Arenz, Stefan, et al.
(författare)
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The stringent factor RelA adopts an open conformation on the ribosome to stimulate ppGpp synthesis
- 2016
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 44:13, s. 6471-6481
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Tidskriftsartikel (refereegranskat)abstract
- Under stress conditions, such as nutrient starvation, deacylated tRNAs bound within the ribosomal A-site are recognized by the stringent factor RelA, which converts ATP and GTP/GDP to (p)ppGpp. The signaling molecules (p) ppGpp globally rewire the cellular transcriptional program and general metabolism, leading to stress adaptation. Despite the additional importance of the stringent response for regulation of bacterial virulence, antibiotic resistance and persistence, structural insight into how the ribosome and deacylated-tRNA stimulate RelA-mediated (p)ppGpp has been lacking. Here, we present a cryo-EM structure of RelA in complex with the Escherichia coli 70S ribosome with an average resolution of 3.7 angstrom and local resolution of 4 to > 10 angstrom for RelA. The structure reveals that RelA adopts a unique 'open' conformation, where the C-terminal domain (CTD) is intertwined around an A/T-like tRNA within the intersubunit cavity of the ribosome and the N-terminal domain (NTD) extends into the solvent. We propose that the open conformation of RelA on the ribosome relieves the autoinhibitory effect of the CTD on the NTD, thus leading to stimulation of (p)ppGpp synthesis by RelA.
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| 4. |
- Ejerhed, Lars, 1951, et al.
(författare)
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Antimicrobial coating is associated with significantly lower aerobic colony counts in high-touch areas in an orthopedic ward environment
- 2020
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Ingår i: Annals of Clinical Microbiology and Antimicrobials. - : Springer Science and Business Media LLC. - 1476-0711. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Hospital acquired infections (HAI) are the most common complication found in the hospital environment. The aim of the study was to examine whether the use of an antimicrobial coating in high-touch areas in an orthopedic ward could reduce bacterial growth and HAI. Methods From December 2017 to February 2018, HAI were registered on two orthopedic wards. A second registration was performed from December 2018 to February 2019. On the second occasion, an antimicrobial organosilane coating was applied just before the study period and thereafter weekly on one ward, while the other ward served as a control. Twenty defined high-touch areas on each ward were cultured before treatment and after 1, 2, 4, 8, 12, 14 and 16 weeks. Samples were cultured for aerobic colony counts, Staphylococcus aureus and E. coli. Results The total aerobic colony counts were 47% lower on the treated ward compared with the non-treated ward over the study period (p = 0.02). The colony counts for Staphylococcus aureus and E. coli were low on both wards. During the first registration period, the incidence of HAI was 22.7% and 20.0% on the non-treated and subsequently treated ward respectively. On the second occasion, after treatment, the incidence was 25.0% and 12.5% (treated ward) respectively (p = 0.0001). Conclusions The use of a long-lasting antimicrobial organosilane coating appears to reduce the bioburden and reduce HAI. Since the incidence of HAI varies substantially over time, longer observation times are needed.
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| 5. |
- Farfaras, Stefanos, et al.
(författare)
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Increased levels of inflammatory markers in the subscapularis tendon and joint capsule in patients with subacromial impingement
- 2021
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 29, s. 2228-2236
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To analyze biopsy samples from the subscapularis tendon and from the joint capsule from male patients with subacromial impingement syndrome and compare them with samples from male patients with post-traumatic recurrent shoulder instability, to detect increased inflammatory activity that might be present inside the humeroscapular joint. Methods Twenty male patients scheduled for surgery for either subacromial decompression or Bankart reconstruction were included. Four biopsies from each patient were obtained during surgery from the capsule and the subscapularis tendon. Each specimen was analyzed for TNF-alpha, IL-6, CD-3 and CD-72. Multiplex fluorescence immunohistochemistry was performed on histological samples from the capsule and tendon to demonstrate the level of inflammatory markers. Fluorescence microscope images were acquired using an automated scanning system. On each slide, the number of pixels was registered and used in the analyses. Results The subacromial impingement syndrome group comprised eight patients, median age 53 (45-74) years, while the instability group 12, median age 27 (22-48) years (p < 0.00001). The amount of IL-6 and TNF-alpha was significantly higher in the subscapularis tendon of the patients with subacromial impingement syndrome compared with instability patients (p = 0.0015 and p = 0.0008 respectively). In the capsular samples, significantly higher amount of TNF-alpha and CD-72 was found in patients with subacromial impingement syndrome compared with instability patients (p < 0.0001 for both). On the other hand, the amount of CD-3 was significantly higher in the instability group (p = 0.0013). Conclusions This study provides evidence that an extended inflammatory process is present, not only in the subacromial bursa but also in the glenohumeral joint in patients with subacromial impingement syndrome.
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| 6. |
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| 7. |
- Kudrin, Pavel, et al.
(författare)
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The ribosomal A-site finger is crucial for binding and activation of the stringent factor RelA
- 2018
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Ingår i: Nucleic Acids Research. - : OXFORD UNIV PRESS. - 0305-1048 .- 1362-4962. ; 46:4, s. 1973-1983
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Tidskriftsartikel (refereegranskat)abstract
- During amino acid starvation the Escherichia coli stringent response factor RelA recognizes deacylated tRNA in the ribosomal A-site. This interaction activates RelA-mediated synthesis of alarmone nucleotides pppGpp and ppGpp, collectively referred to as (p)ppGpp. These two alarmones are synthesized by addition of a pyrophosphate moiety to the 3' position of the abundant cellular nucleotide GTP and less abundant nucleotide GDP, respectively. Using untagged native RelA we show that allosteric activation of RelA by pppGpp increases the efficiency of GDP conversion to achieve the maximum rate of (p) ppGpp production. Using a panel of ribosomal RNA mutants, we show that the A-site finger structural element of 23S rRNA helix 38 is crucial for RelA binding to the ribosome and consequent activation, and deletion of the element severely compromises (p) ppGpp accumulation in E. coli upon amino acid starvation. Through binding assays and enzymology, we show that E. coli RelA does not form a stable complex with, and is not activated by, deacylated tRNA off the ribosome. This indicates that in the cell, RelA first binds the empty A-site and then recruits tRNA rather than first binding tRNA and then binding the ribosome.
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| 8. |
- Odeberg, Jacob, et al.
(författare)
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Cloning and characterization of ZNF189, a novel human Krüppel-like zinc finger gene localized to chromosome 9q22-q31.
- 1998
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 50, s. 233-
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Tidskriftsartikel (refereegranskat)abstract
- A 3-kb-long cDNA encoding a Krüppel-like human zinc finger protein was isolated and mapped to chromosome 9q22-q31. The ZNF189 gene encodes a protein with 16 zinc fingers at its C-terminus and belongs to the Krüppel-associated box (KRAB)-containing group of zinc finger proteins. Four differently spliced cDNA transcripts, differing at the 5' coding region where a KRAB A repressor domain is encoded, were isolated. In addition, Northern blot analysis indicates the presence of two additional unidentified splice variants. Comparison of cDNA and genomic sequences shows that the ZNF189 gene spans approximately 11 kb and is organized into at least four exons, the large 3'-end exon coding for the complete zinc finger domain and the 3' untranslated region. ZNF189 is expressed in all tissues and cell types currently investigated, at varying levels, but with a tissue- or cell-type-restricted expression pattern for the different splice variants. ZNF189 is conserved in the genome of several mammalian species. Direct sequencing of the ZNF189 gene in microdissected tumor biopsies of sporadic basal cell carcinoma and squamous cell carcinoma reveals no mutations in the coding sequence or at exon/intron boundaries.
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| 10. |
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