| 1. |
- Wang, Haidong, et al.
(författare)
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Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013
- 2014
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 384:9947, s. 957-979
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Remarkable financial and political efforts have been focused on the reduction of child mortality during the past few decades. Timely measurements of levels and trends in under-5 mortality are important to assess progress towards the Millennium Development Goal 4 (MDG 4) target of reduction of child mortality by two thirds from 1990 to 2015, and to identify models of success.METHODS: We generated updated estimates of child mortality in early neonatal (age 0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (1-4 years), and under-5 (0-4 years) age groups for 188 countries from 1970 to 2013, with more than 29 000 survey, census, vital registration, and sample registration datapoints. We used Gaussian process regression with adjustments for bias and non-sampling error to synthesise the data for under-5 mortality for each country, and a separate model to estimate mortality for more detailed age groups. We used explanatory mixed effects regression models to assess the association between under-5 mortality and income per person, maternal education, HIV child death rates, secular shifts, and other factors. To quantify the contribution of these different factors and birth numbers to the change in numbers of deaths in under-5 age groups from 1990 to 2013, we used Shapley decomposition. We used estimated rates of change between 2000 and 2013 to construct under-5 mortality rate scenarios out to 2030.FINDINGS: We estimated that 6·3 million (95% UI 6·0-6·6) children under-5 died in 2013, a 64% reduction from 17·6 million (17·1-18·1) in 1970. In 2013, child mortality rates ranged from 152·5 per 1000 livebirths (130·6-177·4) in Guinea-Bissau to 2·3 (1·8-2·9) per 1000 in Singapore. The annualised rates of change from 1990 to 2013 ranged from -6·8% to 0·1%. 99 of 188 countries, including 43 of 48 countries in sub-Saharan Africa, had faster decreases in child mortality during 2000-13 than during 1990-2000. In 2013, neonatal deaths accounted for 41·6% of under-5 deaths compared with 37·4% in 1990. Compared with 1990, in 2013, rising numbers of births, especially in sub-Saharan Africa, led to 1·4 million more child deaths, and rising income per person and maternal education led to 0·9 million and 2·2 million fewer deaths, respectively. Changes in secular trends led to 4·2 million fewer deaths. Unexplained factors accounted for only -1% of the change in child deaths. In 30 developing countries, decreases since 2000 have been faster than predicted attributable to income, education, and secular shift alone.INTERPRETATION: Only 27 developing countries are expected to achieve MDG 4. Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa. The Millennium Declaration and increased development assistance for health might have been a factor in faster decreases in some developing countries. Without further accelerated progress, many countries in west and central Africa will still have high levels of under-5 mortality in 2030.
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| 2. |
- Enciso-Mora, Victor, et al.
(författare)
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Deciphering the 8q24.21 association for glioma
- 2013
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:11, s. 2293-2302
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Tidskriftsartikel (refereegranskat)abstract
- We have previously identified tagSNPs at 8q24.21 influencing glioma risk. We have sought to fine-map the location of the functional basis of this association using data from four genome-wide association studies, comprising a total of 4147 glioma cases and 7435 controls. To improve marker density across the 700 kb region, we imputed genotypes using 1000 Genomes Project data and high-coverage sequencing data generated on 253 individuals. Analysis revealed an imputed low-frequency SNP rs55705857 (P = 2.24 x 10(-38)) which was sufficient to fully capture the 8q24.21 association. Analysis by glioma subtype showed the association with rs55705857 confined to non-glioblastoma multiforme (non-GBM) tumours (P = 1.07 x 10(-67)). Validation of the non-GBM association was shown in three additional datasets (625 non-GBM cases, 2412 controls; P = 1.41 x 10(-28)). In the pooled analysis, the odds ratio for low-grade glioma associated with rs55705857 was 4.3 (P = 2.31 x 10(-94)). rs55705857 maps to a highly evolutionarily conserved sequence within the long non-coding RNA CCDC26 raising the possibility of direct functionality. These data provide additional insights into the aetiological basis of glioma development.
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| 3. |
- Pisarevsky, Sergei A., et al.
(författare)
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Palaeomagnetic, geochronological and geochemical study of Mesoproterozoic Lakhna Dykes in the Bastar Craton, India: Implications for the Mesoproterozoic supercontinent
- 2013
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Ingår i: Lithos. - : Elsevier BV. - 0024-4937. ; 174, s. 125-143
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Tidskriftsartikel (refereegranskat)abstract
- Palaeomagnetic analysis of the Lakhna Dykes (Bastar Craton, India) yields a palaeopole at 36.6 degrees N, 132.8 degrees E, dp=12.4 degrees, dm=15.9 degrees, and the U-Pb zircon age obtained from one of the rhyolitic dykes is 1466.4 +/- 2.6 Ma (MSWD = 0.21, concordia age based on two analyses with identical Pb/U ages), similar to previously published U-Pb ages. Major and trace element analyses of the Lakhna Dykes show shoshonitic and high-K calc-alkaline affinities consistent with a subduction related characteristics suggesting an active continental margin setting. This is in keeping with the Palaeo- to Mesoproterozoic tectonic environments in the eastern Indian margin. The new 1460 Ma Indian palaeopole was used to test possible palaeopositions of India within the Mesoproterozoic supercontinent Columbia. Of the four palaeomagnetically permissible reconstructions, juxtaposing western India against south-west Baltica is geologically the most reliably constrained and best fitting model. Our preferred reconstruction implies a long Palaeo- to Mesoproterozoic accretionary orogen stretching from south-eastern Laurentia through south-western Baltica to south-eastern India. Breakup of India and Baltica probably occurred in the Late Mesoproterozoic, but additional constraints are needed. (C) 2012 Elsevier B.V. All rights reserved.
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| 4. |
- Wang, Rongsheng, et al.
(författare)
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Observation of double layer in the separatrix region during magnetic reconnection
- 2014
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 41:14, s. 4851-4858
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Tidskriftsartikel (refereegranskat)abstract
- We present in situ observation of double layer (DL) and associated electron measurement in the subspin time resolution in the separatrix region during reconnection for the first time. The DL is inferred to propagate away from the X line at a velocity of about ion acoustic speed and the parallel electric field carried by the DL can reach -20 mV/m. The electron displays a beam distribution inside the DL and streams toward the X line with a local electron Alfven velocity. A series of electron holes moving toward the X line are observed in the wake of the DL. The identification of multiple similar DLs indicates that they are persistently produced and therefore might play an important role in energy conversion during reconnection. The observation suggests that energy dissipation during reconnection can occur in any region where the DL can reach.
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| 5. |
- Wang, Xuan, et al.
(författare)
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Bcl-2 maintains the mitochondrial membrane potential, but fails to affect production of reactive oxygen species and endoplasmic reticulum stress, in sodium palmitate-induced beta-cell death
- 2014
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 119:4, s. 306-315
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Tidskriftsartikel (refereegranskat)abstract
- Background. Sodium palmitate causes apoptosis of beta-cells, and the anti-apoptotic protein Bcl-2 has been shown to counteract this event. However, the exact mechanisms that underlie palmitate-induced pancreatic beta-cell apoptosis and through which pathway Bcl-2 executes the protective effect are still unclear. Methods. A stable Bcl-2-overexpressing RINm5F cell clone (BMG) and its negative control (B45) were exposed to palmitate for up to 8 h, and cell viability, mitochondrial membrane potential (Delta psi m), reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress, and NF-kappa B activation were studied in time course experiments. Results. Palmitate exposure for 8 h resulted in increased cell death rates, and this event was partially counteracted by Bcl-2. Bcl-2 overexpression promoted in parallel also a delayed induction of GADD153/CHOP and a weaker phosphorylation of BimEL in palmitate-exposed cells. At earlier time points (2-4 h) palmitate exposure resulted in increased generation of ROS, a decrease in mitochondrial membrane potential (Delta psi m), and a modest increase in the phosphorylation of eIF2 alpha and IRE1 alpha. BMG cells produced similar amounts of ROS and displayed the same eIF2 alpha and IRE1 alpha phosphorylation rates as B45 cells. However, the palmitate-induced dissipation of Delta psi m was partially counteracted by Bcl-2. In addition, basal NF-kappa B activity was increased in BMG cells. Conclusions. Our results indicate that Bcl-2 counteracts palmitate-induced beta-cell death by maintaining mitochondrial membrane integrity and augmenting NF-kappa B activity, but not by affecting ROS production and ER stress.
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| 6. |
- Wang, Xuan, 1984-
(författare)
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Study of the Proliferation, Function and Death of Insulin-Producing Beta-Cells in vitro: Role of the Transcription Factor ZBED6
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A thorough understanding of beta-cell proliferation, function, death and regeneration under normal condition as well as in the progression of diabetes is crucial to the conquest of this disease. The work presented in this thesis aimed to investigate the expression and role of a novel transcription factor, Zinc finger BED domain-containing protein 6 (ZBED6), in beta-cells.ZBED6 was present in mouse βTC-6 cells and human islets as a double nuclear band at 115/120 kDa and as a single cytoplasmic band at 95-100 kDa, which lacked N-terminal nuclear localization signals. Lentiviral shRNA-mediated stable silencing of ZBED6 in βTC-6 cells resulted in altered morphology, decreased proliferation, a partial S/G2 cell cycle arrest, increased expression of beta-cell specific genes, and higher rates of apoptosis. ChIP sequencing of human islets showed that ZBED6 binding was preferentially to genes that control transcription, macromolecule biosynthesis and apoptosis. We proposed that ZBED6 supported proliferation and survival of beta-cells, possibly at the expense of specialized beta-cell function, i.e. insulin production.To further investigate the role of ZBED6 in beta-cells, ChIP sequencing and whole transcriptome analysis were performed using MIN6 cells. More than 4000 putative target genes of ZBED6 were identified, including Pdx1, MafA and Nkx6.1. ZBED6-silencing resulted in differential expression of more than 700 genes, which was paralleled by an increase in the content and release of insulin in response to a high glucose concentration. Altered morphology/growth patterns as indicated by increased cell clustering were observed in ZBED6 silenced cells. We found also that ZBED6 decreased the ratio between N- and E-cadherin. A lower N- to E-cadherin ratio may hamper the formation of three-dimensional beta-cell clusters and cell-to-cell junctions with neural crest stem cells, and instead promote efficient attachment to a laminin support and monolayer growth. Thus, by controlling beta-cell adhesion and cell-to-cell junctions, ZBED6 might play an important role in beta-cell differentiation, proliferation and survival.
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| 7. |
- Wang, Xuan, et al.
(författare)
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Transcription factor ZBED6 affects gene expression, proliferation, and cell death in pancreatic beta cells
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:40, s. 15997-16002
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated whether the recently discovered transcription factor, zinc finger BED domain-containing protein 6 (ZBED6), is expressed in insulin-producing cells and, if so, to what extent it affects beta cell function. ZBED6 was translated from a ZC3H11A transcript in which the ZBED6-containing intron was retained. ZBED6 was present in mouse βTC-6 cells and human islets as a double nuclear band at 115/120 kDa and as a single cytoplasmic band at 95-100 kDa, which lacked N-terminal nuclear localization signals. We propose that ZBED6 supports proliferation and survival of beta cells, possibly at the expense of specialized beta cell function-i.e., insulin production-because (i) the nuclear ZBED6 were the predominant forms in rapidly proliferating βTC-6 cells, but not in human islet cells; (ii) down-regulation of ZBED6 in βTC-6 cells resulted in altered morphology, decreased proliferation, a partial S/G2 cell-cycle arrest, increased expression of beta cell-specific genes, and higher rates of apoptosis; (iii) silencing of ZBED6 in the human PANC-1 duct cell line reduced proliferation rates; and (iv) ZBED6 binding was preferentially to genes that control transcription, macromolecule biosynthesis, and apoptosis. Furthermore, it is possible that beta cells, by switching from full length to a truncated form of ZBED6, can decide the subcellular localization of ZBED6, thereby achieving differential ZBED6-mediated transcriptional regulation.
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