| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Blunden, Jessica, et al.
(författare)
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State of the Climate in 2012
- 2013
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
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Tidskriftsartikel (refereegranskat)abstract
- For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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| 3. |
- Ablikim, M., et al.
(författare)
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Measurement of the $D\to K^-\pi^+$ strong phase difference in $\psi(3770)\to D^0\overline{D}{}^0$
- 2014
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Ingår i: PHYSICS LETTERS B. - : Elsevier BV. - 0370-2693. ; 734
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Tidskriftsartikel (refereegranskat)abstract
- We study $D^0\overline{D}{}^0$ pairs produced in $e^+e^-$ collisions at $\sqrt{s}=3.773$ GeV using a data sample of 2.92 fb$^{-1}$ collected with the BESIII detector. We measure the asymmetry $\mathcal{A}^{CP}_{K\pi}$ of the branching fractions of $D \to K^-\pi^+$ in $CP$-odd and $CP$-even eigenstates to be $(12.7\pm1.3\pm0.7)\times10^{-2}$. $\mathcal{A}^{CP}_{K\pi}$ can be used to extract the strong phase difference $\delta_{K\pi}$ between the doubly Cabibbo-suppressed process $\overline{D}{}^{0}\to K^-\pi^+$ and the Cabibbo-favored process $D^0\to K^- \pi^+$. Using world-average values of external parameters, we obtain $\cos\delta_{K\pi} = 1.02\pm0.11\pm0.06\pm0.01$. Here, the first and second uncertainties are statistical and systematic, respectively, while the third uncertainty arises from the external parameters. This is the most precise measurement of $\delta_{K\pi}$ to date.
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| 4. |
- Ablikim, M., et al.
(författare)
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Observation of e(+)e(-) -> pi(0)pi(0)h(c) and a Neutral Charmoniumlike Structure Z(c)(4020)(0)
- 2014
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 113:21, s. 212002-
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Tidskriftsartikel (refereegranskat)abstract
- Using data collected with the BESIII detector operating at the Beijing Electron Positron Collider at center-of-mass energies of root s = 4.23, 4.26, and 4.36 GeV, we observe e(+)e(-) -> pi(0)pi(0)h(c) for the first time. The Born cross sections are measured and found to be about half of those of e(+)e(-) -> pi(+)pi(-)h(c) within less than 2 sigma. In the pi(0)h(c) mass spectrum, a structure at 4.02 GeV/c(2) is found. It is most likely to be the neutral isospin partner of the Z(c)(4020)(+/-) observed in the process of e(+)e(-) -> pi(+)pi(-)h(c) being found. A fit to the pi(0)h(c) invariant mass spectrum, with the width of the Z(c)(4020)(0) fixed to that of its charged isospin partner and possible interferences with non-Z(c)(4020)(0) amplitudes neglected, gives a mass of (4023.9 +/- 2.2 +/- 3.8) MeV/c(2) for the Z(c)(4020)(0), where the first error is statistical and the second systematic.
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| 5. |
- Ablikim, M., et al.
(författare)
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Observation of $e^+e^− → γX$(3872) at BESIII
- 2014
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Ingår i: PHYSICAL REVIEW LETTERS. - 1079-7114. ; 112:9
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Tidskriftsartikel (refereegranskat)abstract
- With data samples collected with the BESIII detector operating at the BEPCII storage ring at center-of-mass energies from 4.009 to 4.420 GeV, the process $e^{+} e^{-} \to \gamma X(3872)$ is observed for the first time with a statistical significance of $6.3\sigma$. The measured mass of the $X(3872)$ is ($3871.9\pm 0.7_{\rm stat.}\pm 0.2_{\rm sys.}$) MeV/$c^2$, in agreement with previous measurements. Measurements of the product of the cross section $\sigma[e^{+} e^{-} \to \gamma X(3872)]$ and the branching fraction $\mathcal{B}[X(3872) \to \pi^{+} \pi^{-} J/\psi]$ at center-of-mass energies 4.009, 4.229, 4.260, and 4.360 GeV are reported. Our measurements are consistent with expectations for the radiative transition process $Y(4260) \to \gamma X(3872)$.
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| 6. |
- Ablikim, M., et al.
(författare)
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Observation of electromagnetic Dalitz decays J/\psi \to P e^+e^-
- 2014
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Ingår i: PHYSICAL REVIEW D. - 2470-0010 .- 1550-7998 .- 1550-2368. ; 89:9
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Tidskriftsartikel (refereegranskat)abstract
- Based on a sample of (225.3\pm2.8)\times 10^{6} J/\psi events collected with the BESIII detector, the electromagnetic Dalitz decays of J/\psi \to P e^+e^-(P=\eta'/\eta/\pi^0) are studied. By reconstructing the pseudoscalar mesons in various decay modes, the decays J/\psi \to \eta' e^+e^-, J/\psi \to \eta e^+e^- and J/\psi \to \pi^0 e^+e^- are observed for the first time. The branching fractions are determined to be \mathcal{B}(J/\psi\to \eta' e^+e^-) = (5.81\pm0.16\pm0.31)\times10^{-5}, \mathcal{B}(J/\psi\to \eta e^+e^-) = (1.16\pm0.07\pm0.06)\times10^{-5}, and \mathcal{B}(J/\psi\to \pi^0 e^+e^-)=(7.56\pm1.32\pm0.50)\times10^{-7}, where the first errors are statistical and the second ones systematic.
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| 7. |
- Ablikim, M., et al.
(författare)
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Precision measurements of $B(D^+ \rightarrow \mu^+ \nu_{\mu})$, the pseudoscalar decay constant $f_{D^+}$, and the quark mixing matrix element $|V_{\rm cd}|$
- 2014
-
Ingår i: PHYSICAL REVIEW D. - 2470-0010 .- 1550-7998 .- 1550-2368. ; 89:5
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Tidskriftsartikel (refereegranskat)abstract
- We report a measurement of the branching fraction $B(D^+ \rightarrow \mu^+ \nu_{\mu}) = [3.71 \pm 0.19 (\rm stat) \pm 0.06 (\rm sys)]\times 10^{-4}$ based on 2.92 ${\rm fb^{-1}}$ of data accumulated at $\sqrt{s}=3.773$ GeV with the BESIII detector at the BEPCII collider. This measurement, in conjunction with the Cabibbo-Kobayashi-Maskawa matrix element $|V_{\rm cd}|$ determined from a global Standard Model fit, implies a value for the weak decay constant $f_{D^+}=(203.2 \pm 5.3 \pm 1.8)$ MeV. Additionally, using this branching fraction measurement together with a Lattice QCD prediction for $f_{D^+}$, we find $|V_{\rm cd}|=0.2210\pm 0.0058 \pm 0.0047$. In either case, these are the most precise results for these quantities to date.
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| 8. |
- Ablikim, M., et al.
(författare)
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Search for the weak decays J/psi -> D-s(()*()-) e(+)nu(e) + c.c.
- 2014
-
Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 90:11, s. 112014-
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Tidskriftsartikel (refereegranskat)abstract
- Using a sample of 2.25 x 10(8) J/psi events collected with the BESIII detector at the BEPCII collider, we search for the J/psi semileptonic weak decay J/psi -> D-s(-) e(+)nu(e) +c.c. with a much higher sensitivity than previous searches. We also perform the first search for J/psi -> D-s(*-) e(+) nu(e) + c.c. No significant excess of a signal above background is observed in either channel. At the 90% confidence level, the upper limits are determined to be B(J/psi -> D-s(-) e(+) nu(e) + c.c.) < 1.3 x 10(-6) and B(J/psi -> D-s*(-) e(+) nu(e) + c.c.) < 1.8 x 10(-6), respectively. Both are consistent with Standard Model predictions.
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| 9. |
- Blunden, Jessica, et al.
(författare)
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State of the climate in 2013
- 2014
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Ingår i: Bulletin of the American Meteorological Society. - 0003-0007. ; 95
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Tidskriftsartikel (refereegranskat)abstract
- © 2014, American Meteorological Society. All rights reserved. In 2013, the vast majority of the monitored climate variables reported here maintained trends established in recent decades. ENSO was in a neutral state during the entire year, remaining mostly on the cool side of neutral with modest impacts on regional weather patterns around the world. This follows several years dominated by the effects of either La Niña or El Niño events. According to several independent analyses, 2013 was again among the 10 warmest years on record at the global scale, both at the Earth’s surface and through the troposphere. Some regions in the Southern Hemisphere had record or near-record high temperatures for the year. Australia observed its hottest year on record, while Argentina and New Zealand reported their second and third hottest years, respectively. In Antarctica, Amundsen-Scott South Pole Station reported its highest annual temperature since records began in 1957. At the opposite pole, the Arctic observed its seventh warmest year since records began in the early 20th century. At 20-m depth, record high temperatures were measured at some permafrost stations on the North Slope of Alaska and in the Brooks Range. In the Northern Hemisphere extratropics, anomalous meridional atmospheric circulation occurred throughout much of the year, leading to marked regional extremes of both temperature and precipitation. Cold temperature anomalies during winter across Eurasia were followed by warm spring temperature anomalies, which were linked to a new record low Eurasian snow cover extent in May. Minimum sea ice extent in the Arctic was the sixth lowest since satellite observations began in 1979. Including 2013, all seven lowest extents on record have occurred in the past seven years. Antarctica, on the other hand, had above-average sea ice extent throughout 2013, with 116 days of new daily high extent records, including a new daily maximum sea ice area of 19.57 million km2 reached on 1 October. ENSO-neutral conditions in the eastern central Pacific Ocean and a negative Pacific decadal oscillation pattern in the North Pacific had the largest impacts on the global sea surface temperature in 2013. The North Pacific reached a historic high temperature in 2013 and on balance the globally-averaged sea surface temperature was among the 10 highest on record. Overall, the salt content in nearsurface ocean waters increased while in intermediate waters it decreased. Global mean sea level continued to rise during 2013, on pace with a trend of 3.2 mm yr-1 over the past two decades. A portion of this trend (0.5 mm yr-1) has been attributed to natural variability associated with the Pacific decadal oscillation as well as to ongoing contributions from the melting of glaciers and ice sheets and ocean warming. Global tropical cyclone frequency during 2013 was slightly above average with a total of 94 storms, although the North Atlantic Basin had its quietest hurricane season since 1994. In the Western North Pacific Basin, Super Typhoon Haiyan, the deadliest tropical cyclone of 2013, had 1-minute sustained winds estimated to be 170 kt (87.5 m s-1) on 7 November, the highest wind speed ever assigned to a tropical cyclone. High storm surge was also associated with Haiyan as it made landfall over the central Philippines, an area where sea level is currently at historic highs, increasing by 200 mm since 1970. In the atmosphere, carbon dioxide, methane, and nitrous oxide all continued to increase in 2013. As in previous years, each of these major greenhouse gases once again reached historic high concentrations. In the Arctic, carbon dioxide and methane increased at the same rate as the global increase. These increases are likely due to export from lower latitudes rather than a consequence of increases in Arctic sources, such as thawing permafrost. At Mauna Loa, Hawaii, for the first time since measurements began in 1958, the daily average mixing ratio of carbon dioxide exceeded 400 ppm on 9 May. The state of these variables, along with dozens of others, and the 2013 climate conditions of regions around the world are discussed in further detail in this 24th edition of the State of the Climate series.
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| 10. |
- Chen, Peng, et al.
(författare)
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Assembly of Graphene Oxide and Au(0.7)Ag(0.3) Alloy Nanoparticles on SiO(2): A New Raman Substrate with Ultrahigh Signal-to-Background Ratio
- 2011
-
Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society. - 1932-7447 .- 1932-7455. ; 115:49, s. 24080-24084
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Tidskriftsartikel (refereegranskat)abstract
- Resonance Raman spectroscopy (RRS) often suffers from the large fluorescence background which obscures the much weaker Raman scattering. To address this fundamental problem, a novel Raman substrate has been fabricated by adsorption of Au(0.7)Ag(0.3) alloy nanoparticles (NPs) on a graphene oxide (GO) coated SiO(2) surface, which offers both excellent Raman enhancement and fluorescence quenching. Our experimental data reveal that a Raman to fluorescence background intensity ratio of 1.6 can be obtained for a highly fluorescent dye like Alexa fluor 488. Moreover, we demonstrate that the Raman enhancement mainly originates from the Au(0.7)Ag(0.3) alloy NPs and that the fluorescence quenching mainly arises from the underlying functionalized GO (FGO) substrate.
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| 11. |
- Cho, Yoon Shin, et al.
(författare)
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Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:1
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
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| 12. |
- Deng, Min, et al.
(författare)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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| 13. |
- Peng, Yanling, et al.
(författare)
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Phylogeographic analysis of the fir species in southern China suggests complex origin and genetic admixture
- 2012
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Ingår i: Annals of Forest Science. - 1286-4560 .- 1297-966X. ; 69:3, s. 409-416
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Tidskriftsartikel (refereegranskat)abstract
- ContextFir species are mainly distributed across the high latitudes, preferring cold climates. The phylogeographic origins of those subtropical fir species that occur in low latitudes in southern China remain elusive, as does the nature of any inter-lineage hybridization.AimsIn fir species, mitochondrial DNA (mtDNA) is mater- nally inherited and chloroplast DNA (cpDNA) is paternally inherited, and the genetic variations in the two make them particularly useful for examining species’ hybridizations and evolutionary histories.Materialsand methods We sequenced four DNA frag- ments: two of mtDNA and two of cpDNA for 161 individuals from four subtropical endangered fir species (Abies beshan- zuensis, Abies ziyuanensis, Abies yuanbaoshanensis, and Abies fanjingshanensis) and two more northerly distributed ones (Abies recurvata and Abies fargesii) from central and southwest China.ResultsThree mitotypes and four chlorotypes were recov- ered from the four southern species. In most populations, individuals share a single fixed mitotype and chlorotype. Three mitotypes clustered into two distinct clades, each associated with one of the northern species examined. For four chlorotypes, one occurred in A. ziyuanensis, A. beshan- zuensis, A. fargesii, and A. recurvata, another in A. ziyua- nensis and A. recurvata, the remaining two differed from others by two mutations exclusively in A. fanjingshanenis and A. yuanbaoshanensis.ConclusionPhylogeographic origins of the subtropical fir species are complex, and genetic admixtures occurred dur- ing the evolutionary history of A. ziyuanensis. The geno- typed populations further provide basic frames for genetic delimitation and effective conservation of these endangered species in the future.
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| 14. |
- Piao, Shilong, et al.
(författare)
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Evidence for a weakening relationship between interannual temperature variability and northern vegetation activity.
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Satellite-derived Normalized Difference Vegetation Index (NDVI), a proxy of vegetation productivity, is known to be correlated with temperature in northern ecosystems. This relationship, however, may change over time following alternations in other environmental factors. Here we show that above 30°N, the strength of the relationship between the interannual variability of growing season NDVI and temperature (partial correlation coefficient RNDVI-GT) declined substantially between 1982 and 2011. This decrease in RNDVI-GT is mainly observed in temperate and arctic ecosystems, and is also partly reproduced by process-based ecosystem model results. In the temperate ecosystem, the decrease in RNDVI-GT coincides with an increase in drought. In the arctic ecosystem, it may be related to a nonlinear response of photosynthesis to temperature, increase of hot extreme days and shrub expansion over grass-dominated tundra. Our results caution the use of results from interannual time scales to constrain the decadal response of plants to ongoing warming.
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| 15. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 16. |
- Wang, Zhongli, et al.
(författare)
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Prevalence and associated metabolic factors of fatty liver disease in the elderly
- 2013
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Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 48:8, s. 705-709
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to investigate the metabolic risk factors for fatty liver disease in the elderly, and determine the prevalence of fatty liver disease in the elderly in Wuhan, central China.METHODS: The study was a case-control study based on all 4226 adults above 60years of age from a cohort investigated in 2010-11 at the medical examination center of Zhongnan hospital, using 3145 randomly selected adults under 60years of age from the same cohort as controls. Fatty liver disease (FLD) was identified with ultrasound imaging. The risk factors measured were body mass index (BMI), and plasma concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low density lipoprotein (LDL) and serum uric acid (SUA). The probability of steatohepatitis with advanced fibrosis was predicted using a score based on BMI, age, ALT, and TG (BAAT),and using AST/ALT ratio (AAR).RESULTS: FLD was higher in the elderly (26.7%) than in the non-elderly (22.8%) and similar in the elderly between men and women (26.6% vs 27.0%, p>0.05). BMI, TC, TG, LDL, SUA, AST and ALT were all significantly higher in FLD, whereas the level of HDL was markedly lower. Multiple regression analyses showed that obesity, high TC, TG, SUA, low HDL, and elevated ALT, AAR<1 were closely related to the elderly FLD, while male sex, obesity, high TC, TG, low HDL, elevated ALT, AST and AAR<1 were closely related to the non-elderly FLD. The prevalence of steatohepatitis with advanced fibrosis estimated as BAAT index≥3 was 2.4% in all subjects, and was higher in the elderly FLD patients than in the non-elderly FLD patients.CONCLUSION: The prevalence of FLD is higher in the elderly, and is broadly related to the same metabolic risk factors as in the non-elderly. However, female-sex is no longer protective with increasing age, and the prevalence of steatohepatitis with advanced fibrosis is estimated to be considerably higher in the elderly FLD patients than in the non-elderly FLD controls.
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| 17. |
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