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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)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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| 3. |
- Dong, Yu, et al.
(author)
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Observation of a Ubiquitous (π, π)-Type Nematic Superconducting Order in the Whole Superconducting Dome of Ultra-Thin BaFe2–xNixAs2 Single Crystals
- 2021
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In: Chinese Physics Letters. - : Institute of Physics Publishing (IOPP). - 0256-307X .- 1741-3540. ; 38:9
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Journal article (peer-reviewed)abstract
- In iron-based superconductors, the (0, pi) or (pi, 0) nematicity, which describes an electronic anisotropy with a four-fold symmetry breaking, is well established and believed to be important for understanding the superconducting mechanism. However, how exactly such a nematic order observed in the normal state can be related to the superconducting pairing is still elusive. Here, by performing angular-dependent in-plane magnetoresistivity using ultra-thin flakes in the steep superconducting transition region, we unveil a nematic superconducting order along the (pi, pi) direction in electron-doped BaFe2 - x Ni x As2 from under-doped to heavily overdoped regimes with x = 0.065-0.18. It shows superconducting gap maxima along the (pi, pi) direction rotated by 45 degrees from the nematicity along (0, pi) or (pi, 0) direction observed in the normal state. A similar (pi, pi)-type nematicity is also observed in the under-doped and optimally doped hole-type Ba1 - y K y Fe2As2, with y = 0.2-0.5. These results suggest that the (pi, pi) nematic superconducting order is a universal feature that needs to be taken into account in the superconducting pairing mechanism in iron-based superconductors.
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| 6. |
- Calabrese, Claudia, et al.
(author)
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Genomic basis for RNA alterations in cancer
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578:7793, s. 129-136
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Journal article (peer-reviewed)abstract
- Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.
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| 7. |
- Feng, Kui, et al.
(author)
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Fused Bithiophene Imide Dimer-Based n-Type Polymers for High-Performance Organic Electrochemical Transistors
- 2021
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In: Angewandte Chemie International Edition. - : WILEY-V C H VERLAG GMBH. - 1433-7851 .- 1521-3773. ; 60:45, s. 24198-24205
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Journal article (peer-reviewed)abstract
- The development of n-type organic electrochemical transistors (OECTs) lags far behind their p-type counterparts. In order to address this dilemma, we report here two new fused bithiophene imide dimer (f-BTI2)-based n-type polymers with a branched methyl end-capped glycol side chain, which exhibit good solubility, low-lying LUMO energy levels, favorable polymer chain orientation, and efficient ion transport property, thus yielding a remarkable OECT electron mobility (mu(e)) of up to approximate to 10(-2) cm(2) V-1 s(-1) and volumetric capacitance (C*) as high as 443 F cm(-3), simultaneously. As a result, the f-BTI2TEG-FT-based OECTs deliver a record-high maximum geometry-normalized transconductance of 4.60 S cm(-1) and a maximum mu C* product of 15.2 F cm(-1) V-1 s(-1). The mu C* figure of merit is more than one order of magnitude higher than that of the state-of-the-art n-type OECTs. The emergence of f-BTI2TEG-FT brings a new paradigm for developing high-performance n-type polymers for low-power OECT applications.
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| 8. |
- Georgiou, Konstantinos, et al.
(author)
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Genetic basis of PD-L1 overexpression in diffuse large B-cell lymphomas
- 2016
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 127:24, s. 3026-3034
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Journal article (peer-reviewed)abstract
- Diffuse large B-cell lymphoma (DLBCL) is one of the most common and aggressive types of B-cell lymphoma. Deregulation of proto-oncogene expression after a translocation, most notably to the immunoglobulin heavy-chain locus (IGH), is one of the hallmarks of DLBCL. Using whole-genome sequencing analysis, we have identified the PD-L1/PD-L2 locus as a recurrent translocation partner for IGH in DLBCL. PIM1 and TP63 were also identified as novel translocation partners for PD-L1/PD-L2. Fluorescence in situ hybridization was furthermore used to rapidly screen an expanded DLBCL cohort. Collectively, a subset of samples was found to be affected by gains (12%), amplifications (3%), and translocations (4%) of the PD-L1/PD-L2 locus. RNA sequencing data coupled with immunohistochemistry revealed that these cytogenetic alterations correlated with increased expression of PD-L1 but not of PD-L2. Moreover, cytogenetic alterations affecting the PD-L1/PD-L2 locus were more frequently observed in the non-germinal center B cell-like (non-GCB) subtype of DLBCL. These findings demonstrate the genetic basis of PD-L1 overexpression in DLBCL and suggest that treatments targeting the PD-1-PD-L1/PD-L2 axis might benefit DLBCL patients, especially those belonging to the more aggressive non-GCB subtype.
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| 9. |
- Guo, Han, et al.
(author)
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Transition metal-catalysed molecular n-doping of organic semiconductors
- 2021
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In: Nature. - London, United Kingdom : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 599:7883, s. 67-73
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Journal article (peer-reviewed)abstract
- Electron doping of organic semiconductors is typically inefficient, but here a precursor molecular dopant is used to deliver higher n-doping efficiency in a much shorter doping time. Chemical doping is a key process for investigating charge transport in organic semiconductors and improving certain (opto)electronic devices(1-9). N(electron)-doping is fundamentally more challenging than p(hole)-doping and typically achieves a very low doping efficiency (eta) of less than 10%(1,10). An efficient molecular n-dopant should simultaneously exhibit a high reducing power and air stability for broad applicability(1,5,6,9,11), which is very challenging. Here we show a general concept of catalysed n-doping of organic semiconductors using air-stable precursor-type molecular dopants. Incorporation of a transition metal (for example, Pt, Au, Pd) as vapour-deposited nanoparticles or solution-processable organometallic complexes (for example, Pd-2(dba)(3)) catalyses the reaction, as assessed by experimental and theoretical evidence, enabling greatly increased eta in a much shorter doping time and high electrical conductivities (above 100 S cm(-1); ref. (12)). This methodology has technological implications for realizing improved semiconductor devices and offers a broad exploration space of ternary systems comprising catalysts, molecular dopants and semiconductors, thus opening new opportunities in n-doping research and applications(12, 13).
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| 10. |
- Jarvis, Erich D., et al.
(author)
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Whole-genome analyses resolve early branches in the tree of life of modern birds
- 2014
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1320-1331
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Journal article (peer-reviewed)abstract
- To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
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