Nobel Lecture, presented December 8, 2016, Aula Magna, Stockholm University. I will describe the history and background of three discoveries cited in this Nobel Prize: The “TKNN” topological formula ...for the integer quantum Hall effect found by David Thouless and collaborators, the Chern insulator or quantum anomalous Hall effect, and its role in the later discovery of time-reversal-invariant topological insulators, and the unexpected topological spin-liquid state of the spin-1 quantum antiferromagnetic chain, which provided an initial example of topological quantum matter. I will summarize how these early beginnings have led to the exciting, and currently extremely active, field of “topological matter.”
In addition to their being vital components of mid- to high-latitude coastal ecosystems, salt marshes contain 0.1% of global sequestered terrestrial carbon. Their sustainability is now threatened by ...accelerating sea-level rise (SLR) that has reached a rate that is many times greater than the rate at which they formed and evolved. Modeling studies have been instrumental in predicting how marsh systems will respond to greater frequencies and durations of tidal inundation and in quantifying thresholds when marshes will succumb and begin to disintegrate due to accelerating SLR. Over the short term, some researchers believe that biogeomorphic feedbacks will improve marsh survival through greater biomass productivity enhanced by warmer temperatures and higher carbon dioxide concentrations. Increased sedimentation rates are less likely due to lower-than-expected suspended sediment concentrations. The majority of marsh loss today is through wave-induced edge erosion that beneficially adds sediment to the system. Edge erosion is partly offset by upland marsh migration during SLR.
Despite positive biogeomorphic feedbacks, many salt marshes will succumb to accelerating sea-level rise due to insufficient mineral sediment.
The latest multivariate marsh modeling is producing predictions of marsh evolution under various sea-level rise scenarios.
The least well-known variables in projecting changes to salt marshes are suspended sediment concentrations and net sediment influx to the marsh.
We are in the infancy of understanding the importance and processes of marsh edge erosion and the overall dynamicism of marshes.
This review defines the latest breakthroughs in understanding the response of salt marshes to accelerating sea-level rise and decreasing sediment supply.
Climate change is accelerating sea-level rise, warming temperatures, and increasing carbon dioxide, all of which are impacting marsh vegetation and vertical accretion.
Telomeres and genomic evolution Baird, Duncan M.
Philosophical transactions - Royal Society. Biological sciences,
03/2018, Letnik:
373, Številka:
1741
Journal Article
Recenzirano
Odprti dostop
The terminal regions of eukaryotic chromosomes, composed of telomere repeat sequences and sub-telomeric sequences, represent some of the most variable and rapidly evolving regions of the genome. The ...sub-telomeric regions are characterized by segmentally duplicated repetitive DNA elements, interstitial telomere repeat sequences and families of variable genes. Sub-telomeric repeat sequence families are shared among multiple chromosome ends, often rendering detailed sequence characterization difficult. These regions are composed of constitutive heterochromatin and are subjected to high levels of meiotic recombination. Dysfunction within telomere repeat arrays, either due to disruption in the chromatin structure or because of telomere shortening, can lead to chromosomal fusion and the generation of large-scale genomic rearrangements across the genome. The dynamic nature of telomeric regions, therefore, provides functionally useful variation to create genetic diversity, but also provides a mechanism for rapid genomic evolution that can lead to reproductive isolation and speciation. This article is part of the theme issue ‘Understanding diversity in telomere dynamics'.
This article is part of the theme issue ‘Understanding diversity in telomere dynamics’.
Implementing new practices requires changes in the behaviour of relevant actors, and this is facilitated by understanding of the determinants of current and desired behaviours. The Theoretical ...Domains Framework (TDF) was developed by a collaboration of behavioural scientists and implementation researchers who identified theories relevant to implementation and grouped constructs from these theories into domains. The collaboration aimed to provide a comprehensive, theory-informed approach to identify determinants of behaviour. The first version was published in 2005, and a subsequent version following a validation exercise was published in 2012. This guide offers practical guidance for those who wish to apply the TDF to assess implementation problems and support intervention design. It presents a brief rationale for using a theoretical approach to investigate and address implementation problems, summarises the TDF and its development, and describes how to apply the TDF to achieve implementation objectives. Examples from the implementation research literature are presented to illustrate relevant methods and practical considerations.
Researchers from Canada, the UK and Australia attended a 3-day meeting in December 2012 to build an international collaboration among researchers and decision-makers interested in the advancing use of the TDF. The participants were experienced in using the TDF to assess implementation problems, design interventions, and/or understand change processes. This guide is an output of the meeting and also draws on the authors' collective experience. Examples from the implementation research literature judged by authors to be representative of specific applications of the TDF are included in this guide.
We explain and illustrate methods, with a focus on qualitative approaches, for selecting and specifying target behaviours key to implementation, selecting the study design, deciding the sampling strategy, developing study materials, collecting and analysing data, and reporting findings of TDF-based studies. Areas for development include methods for triangulating data, e.g. from interviews, questionnaires and observation and methods for designing interventions based on TDF-based problem analysis.
We offer this guide to the implementation community to assist in the application of the TDF to achieve implementation objectives. Benefits of using the TDF include the provision of a theoretical basis for implementation studies, good coverage of potential reasons for slow diffusion of evidence into practice and a method for progressing from theory-based investigation to intervention.
When cells progress to malignancy, they must overcome a final telomere-mediated proliferative lifespan barrier called replicative crisis. Crisis is characterized by extensive telomere fusion that ...drives widespread genomic instability, mitotic arrest, hyperactivation of autophagy, and cell death. Recently, it has become apparent that that the resolution of dicentric chromosomes, which arise from telomere fusions during crisis, can initiate a sequence of events that leads to chromothripsis, a form of extreme genomic catastrophe. Chromothripsis is characterized by localized genomic regions containing tens to thousands of rearrangements and it is becoming increasingly apparent that chromothripsis occurs widely across tumor types and has a clinical impact. Here we discuss how telomere dysfunction can initiate genomic complexity and the emerging mechanisms of chromothripsis.
Short dysfunctional telomeres are subjected to fusion with loci across the genome and this leads to the formation of dicentric chromosomes.Breakage of dicentric chromosomes during cell division leads to simple large-scale deletions and insertions, but complex chromothriptic events can also arise.A single dysfunctional telomere can initiate a cascade of events that leads to chromothripsis.It appears that multiple mechanisms underpin chromothripsis-like events, involving micronuclei-dependent and -independent routes and utilizing non-homologous end-joining or replicative repair pathways.The mutational profile of telomere-driven chromothripsis is consistent with replicative repair processes.
Finding faster and simpler ways to screen protein sequence space to enable the identification of new biocatalysts for asymmetric synthesis remains both a challenge and a rate-limiting step in enzyme ...discovery. Biocatalytic strategies for the synthesis of chiral amines are increasingly attractive and include enzymatic asymmetric reductive amination, which offers an efficient route to many of these high-value compounds. Here we report the discovery of over 300 new imine reductases and the production of a large (384 enzymes) and sequence-diverse panel of imine reductases available for screening. We also report the development of a facile high-throughput screen to interrogate their activity. Through this approach we identified imine reductase biocatalysts capable of accepting structurally demanding ketones and amines, which include the preparative synthesis of N-substituted β-amino ester derivatives via a dynamic kinetic resolution process, with excellent yields and stereochemical purities.
Structural variation (SV) plays a fundamental role in genome evolution and can underlie inherited or acquired diseases such as cancer. Long-read sequencing technologies have led to improvements in ...the characterization of structural variants (SVs), although paired-end sequencing offers better scalability. Here, we present dysgu, which calls SVs or indels using paired-end or long reads. Dysgu detects signals from alignment gaps, discordant and supplementary mappings, and generates consensus contigs, before classifying events using machine learning. Additional SVs are identified by remapping of anomalous sequences. Dysgu outperforms existing state-of-the-art tools using paired-end or long-reads, offering high sensitivity and precision whilst being among the fastest tools to run. We find that combining low coverage paired-end and long-reads is competitive in terms of performance with long-reads at higher coverage values.
ATP synthase is a membrane-bound rotary motor enzyme that is critical for cellular energy metabolism in all kingdoms of life. Despite conservation of its basic structure and function, autoinhibition ...by one of its rotary stalk subunits occurs in bacteria and chloroplasts but not in mitochondria. The crystal structure of the ATP synthase catalytic complex (F(1)) from Escherichia coli described here reveals the structural basis for this inhibition. The C-terminal domain of subunit ɛ adopts a heretofore unknown, highly extended conformation that inserts deeply into the central cavity of the enzyme and engages both rotor and stator subunits in extensive contacts that are incompatible with functional rotation. As a result, the three catalytic subunits are stabilized in a set of conformations and rotational positions distinct from previous F(1) structures.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Treatment with immune checkpoint blockade (CPB) therapies often leads to prolonged responses in patients with metastatic melanoma, but the common mechanisms of primary and acquired resistance to ...these agents remain incompletely characterized and have yet to be validated in large cohorts. By analyzing longitudinal tumor biopsies from 17 metastatic melanoma patients treated with CPB therapies, we observed point mutations, deletions or loss of heterozygosity (LOH) in beta-2-microglobulin (B2M), an essential component of MHC class I antigen presentation, in 29.4% of patients with progressing disease. In two independent cohorts of melanoma patients treated with anti-CTLA4 and anti-PD1, respectively, we find that B2M LOH is enriched threefold in non-responders (~30%) compared to responders (~10%) and associated with poorer overall survival. Loss of both copies of B2M is found only in non-responders. B2M loss is likely a common mechanism of resistance to therapies targeting CTLA4 or PD1.
The prevalence of children with elevated weight or obesity is concerning for public health due to associated comorbidities. This study investigates associations between parental adiposity, physical ...activity (PA), fruit and vegetable consumption, and child adiposity and moderation by both child and parent gender.
Cross-sectional nationally representative data from the New Zealand Health Survey were pooled for the years 2013/14-2016/17. Parent and child surveys were matched resulting in 13,039 child (2-14 years) and parent (15-70 years) dyads. Parent and child, height (cm), weight (kg) and waist circumference (WC) were measured objectively. Height and weight were used to calculate BMI. Linear regression, accounting for clustered samples (b 95% CI) investigated associations between parental characteristics and child BMI z-score and WC. Interactions and stratification were used to investigate effect moderation by parent gender, child gender, and parent adiposity.
Parental PA and fruit and vegetable consumption were unrelated to child adiposity. Overall, higher parent BMI was related to a higher child BMI z-score (b = 0.047 0.042, 0.052) and higher parental WC was related to a higher child WC (0.15 0.12, 0.17). A three-way interaction revealed no moderation by parent gender, child gender, and parent BMI for child BMI z-score ((b = 0.005 -0.017, 0.027, p = 0.318). However, a three-way interaction revealed moderation by parent gender, child gender, and parent WC for child WC (b = 0.13 0.05, 0.22). The slightly stronger associations were seen between father-son WC (b = 0.20 0.15, 0.24) and mother-daughter WC (b = 0.19 0.15, 0.22).
The findings are highly relevant for those wishing to understand the complex relationships between child-parent obesity factors. Findings suggest that family environments should be a key target for obesity intervention efforts and show how future public health interventions should be differentiated to account for both maternal and paternal influences on child adiposity.
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