| 1. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
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.
|
|
| 2. |
- Wang, Zhaoming, et al.
(författare)
-
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
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
-
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.
|
|
| 3. |
- Blunden, Jessica, et al.
(författare)
-
State of the Climate in 2012
- 2013
-
Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
-
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.
|
|
| 4. |
- Sui, Jiong-Ming, et al.
(författare)
-
Isolation and characterization of a stress responsive small GTP-binding protein AhRabG3b in peanut (Arachis hypogaea L.)
- 2013
-
Ingår i: Euphytica. - : Springer Science and Business Media LLC. - 0014-2336 .- 1573-5060. ; 189:2, s. 161-172
-
Tidskriftsartikel (refereegranskat)abstract
- Rab7 is a member of small GTP-binding protein family involved in intracellular vesicle trafficking from late endosome to vacuole, some of them are found to be responsive by different environmental stresses. Here we report the isolation of a Rab7 (RabG3b) cDNA from peanut (Arachis hypogaea). Overexpression of the open reading frame (ORF) of Rab7 cDNA encoding 205 amino acids in E. coli conferred the cells tolerance to various abiotic stresses. Transcription of AhRabG3b was differentially up-regulated by different environmental stimuli such as cold, dehydration, NaCl and the plant hormone ABA. Overexpression of the AhRabG3b exhibited enhanced tolerance to drought and salinity stresses in transgenic peanut. These results suggested that the AhRabG3b be a potential candidate gene responsible for both salinity and dehydration tolerance in cultivated peanut.
|
|
| 5. |
- Yu, Di, et al.
(författare)
-
Adenovirus Serotype 5 Vectors with Tat-PTD Modified Hexon and Serotype 35 Fiber Show Greatly Enhanced Transduction Capacity of Primary Cell Cultures
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1, s. e54952-
-
Tidskriftsartikel (refereegranskat)abstract
- Recombinant adenovirus serotype 5 (Ad5) vectors represent one of the most efficient gene delivery vectors in life sciences. However, Ad5 is dependent on expression of the coxsackievirus-adenovirus- receptor (CAR) on the surface of target cell for efficient transduction, which limits it's utility for certain cell types. Herein we present a new vector, Ad5PTDf35, which is an Ad5 vector having serotype 35 fiber-specificity and Tat-PTD hexon-modification. This vector shows dramatically increased transduction capacity of primary human cell cultures including T cells, monocytes, macrophages, dendritic cells, pancreatic islets and exocrine cells, mesenchymal stem cells and tumor initiating cells. Biodistribution in mice following systemic administration (tail-vein injection) show significantly reduced uptake in the liver and spleen of Ad5PTDf35 compared to unmodified Ad5. Therefore, replication-competent viruses with these modifications may be further developed as oncolytic agents for cancer therapy. User-friendly backbone plasmids containing these modifications were developed for compatibility to the AdEasy-system to facilitate the development of surface-modified adenoviruses for gene delivery to difficult-to-transduce cells in basic, pre-clinical and clinical research.
|
|
| 6. |
- Zhang, Yan, 1976, et al.
(författare)
-
Experimental and Numerical Investigations on the Performance and Reliability of CNT Fins for Micro-Cooler
- 2012
-
Ingår i: Proceedings of IEEE CPMT 2012 International Conference on Electronic Packaging Technology & High Density Packaging. - 9781467316804 ; , s. 1573-1577
-
Konferensbidrag (refereegranskat)abstract
- The current development of electronic products towards miniaturization and multifunction is leading to an increase in the power density of chip and IC. The high power consumption and corresponding heat dissipation are two of the most serious limitations for high performance electronics. The combination of the carbon nanotube (CNT) with outstanding thermal properties with an air jet cooling provides a promising option for the heat dissipation of high-powered components and devices. In the present paper, the CNTs are utilized to manufacture the pin-fins for the micro-cooler, and the performance and evaluation of this CNT-based micro-pin-fin cooler are investigated both experimentally and numerically. The effects of various parameters, such as the jet velocity and height, the fin size and shape, and so on, on the flow field and temperature distribution characteristics are comprehensively considered and analyzed. The obtained results indicate that the CNT-fins are of quite good strength and thermal performance in the jet impingement cooling environment. © 2012 IEEE.
|
|
| 7. |
- Zhang, Y., et al.
(författare)
-
Experimental measurements for mechanical and electrical conductive properties of CNT bundles
- 2013
-
Ingår i: 6th International Conference on Nonlinear Mechanics, ICNM 2013; Shanghai; China; 12 August 2013 through 15 August 2013. - 9781605951096 ; , s. 454-457
-
Konferensbidrag (refereegranskat)abstract
- With the miniaturization and multifunction trend in consumer electronics and other numerous applications, the characteristic sizes of chips, components and devices become smaller and smaller while the power dissipation and the associated heat flux density increase constantly. Carbon nanotube (CNT) has become a promising material due to its mechanical and conductive properties. In this paper, the CNT bundles on silicon chip have been experimentally investigated with respect to both the mechanical behavior under loading and the electrical conductivity as flip-chip interconnects.
|
|
| 8. |
- Zhang, Yan, et al.
(författare)
-
Numerical investigation on thermal properties of micro-pin-fin cooler
- 2011
-
Ingår i: Journal of Shanghai University. - 1007-6417. ; 15:4, s. 273 - 278
-
Tidskriftsartikel (refereegranskat)abstract
- Micro-pin-fin cooler mounted on the power chip enables the heat removal to meet modern microsystem requirement. Carbon nanotubes (CNTs) have been proven as a potential material for micro-coolers due to the superior thermal conductivity, good mechanical property and so forth, and there appear various applications of CNTs in the micro-cooler technology. In the present paper, an analysis of the thermal and hydraulic characteristics of the micro-pin-fin heat sink was conducted, where air was used as the cooling medium and an impinging jet was introduced to enhance the heat transfer. Three-dimension computational fluid dynamics (CFD) simulations were carried out for micro-pin-fin coolers with various parameters, including the pin-fin size and pattern as well as the jet velocity and nozzle diameter. The flow field and thermal properties of the micro-pin-fin heat sink were obtained, and the heat removal efficiency was evaluated.
|
|
| 9. |
- Zhang, Y., et al.
(författare)
-
Study on the bimodal filler influence on the effective thermal conductivity of thermal conductive adhesive
- 2011
-
Ingår i: Microsystem Technologies. - : Springer Science and Business Media LLC. - 0946-7076 .- 1432-1858. ; 17:1, s. 93-99
-
Tidskriftsartikel (refereegranskat)abstract
- The thermal management for electronics systems becomes more crucial to the overall system performance as the packaging density becomes much higher and the IC power increases at the same time. Thermal conductive adhesives (TCAs) have been widely adopted in electronics systems. As an epoxy matrix with conductive fillers, it is essential to figure out the effective thermal conductivity of this composite material. In the present paper, a parameterized cubic cell model (CCM) is developed and then implemented by the finite element method to investigate the effects of the bimodal fillers on the effective thermal conductivity. In addition, a series of bimodal TCA samples are prepared and the thermal conductivities in the in-plane and vertical directions are measured experimentally. An obvious anisotropy with respect to the thermal conductivities has been observed for the bimodal filler loading under consideration. A good agreement between the numerical results and the experimental data is obtained.
|
|
