Single-molecule real-time sequencing combined with optical mapping yields completely finished fungal genome

Next-generation sequencing (NGS) technologies have increased the scalability, speed, and resolution of genomic sequencing and, thus, have revolutionized genomic studies. However, eukaryotic genome sequencing initiatives typically yield considerably fragmented genome assemblies. Here, we assessed various state-of-the-art sequencing and assembly strategies in order to produce a contiguous and complete eukaryotic genome assembly, focusing on the filamentous fungus Verticillium dahliae. Compared with Illumina-based assemblies of the V. dahliae genome, hybrid assemblies that also include PacBio- generated long reads establish superior contiguity. Intriguingly, provided that sufficient sequence depth is reached, assemblies solely based on PacBio reads outperform hybrid assemblies and even result in fully assembled chromosomes. Furthermore, the addition of optical map data allowed us to produce a gapless and complete V. dahliae genome assembly of the expected eight chromosomes from telomere to telomere. Consequently, we can now study genomic regions that were previously not assembled or poorly assembled, including regions that are populated by repetitive sequences, such as transposons, allowing us to fully appreciate an organism’s biological complexity. Our data show that a combination of PacBio-generated long reads and optical mapping can be used to generate complete and gapless assemblies of fungal genomes. IMPORTANCE Studying whole-genome sequences has become an important aspect of biological research. The advent of nextgeneration sequencing (NGS) technologies has nowadays brought genomic science within reach of most research laboratories, including those that study nonmodel organisms. However, most genome sequencing initiatives typically yield (highly) fragmented genome assemblies. Nevertheless, considerable relevant information related to genome structure and evolution is likely hidden in those nonassembled regions. Here, we investigated a diverse set of strategies to obtain gapless genome assemblies, using the genome of a typical ascomycete fungus as the template. Eventually, we were able to show that a combination of PacBiogenerated long reads and optical mapping yields a gapless telomere-to-telomere genome assembly, allowing in-depth genome sanalyses to facilitate functional studies into an organism’s biology

Spike Timing Dependent Plasticity: A Consequence of More Fundamental Learning Rules

Spike timing dependent plasticity (STDP) is a phenomenon in which the precise timing of spikes affects the sign and magnitude of changes in synaptic strength. STDP is often interpreted as the comprehensive learning rule for a synapse – the “first law” of synaptic plasticity. This interpretation is made explicit in theoretical models in which the total plasticity produced by complex spike patterns results from a superposition of the effects of all spike pairs. Although such models are appealing for their simplicity, they can fail dramatically. For example, the measured single-spike learning rule between hippocampal CA3 and CA1 pyramidal neurons does not predict the existence of long-term potentiation one of the best-known forms of synaptic plasticity. Layers of complexity have been added to the basic STDP model to repair predictive failures, but they have been outstripped by experimental data. We propose an alternate first law: neural activity triggers changes in key biochemical intermediates, which act as a more direct trigger of plasticity mechanisms. One particularly successful model uses intracellular calcium as the intermediate and can account for many observed properties of bidirectional plasticity. In this formulation, STDP is not itself the basis for explaining other forms of plasticity, but is instead a consequence of changes in the biochemical intermediate, calcium. Eventually a mechanism-based framework for learning rules should include other messengers, discrete change at individual synapses, spread of plasticity among neighboring synapses, and priming of hidden processes that change a synapse's susceptibility to future change. Mechanism-based models provide a rich framework for the computational representation of synaptic plasticity

Inferred changes in El Niño–Southern Oscillation variance over the past six centuries

It is vital to understand how the El Niño–Southern Oscillation (ENSO) has responded to past changes in natural and anthropogenic forcings, in order to better understand and predict its response to future greenhouse warming. To date, however, the instrumental record is too brief to fully characterize natural ENSO variability, while large discrepancies exist amongst paleo-proxy reconstructions of ENSO. These paleo-proxy reconstructions have typically attempted to reconstruct ENSO's temporal evolution, rather than the variance of these temporal changes. Here a new approach is developed that synthesizes the variance changes from various proxy data sets to provide a unified and updated estimate of past ENSO variance. The method is tested using surrogate data from two coupled general circulation model (CGCM) simulations. It is shown that in the presence of dating uncertainties, synthesizing variance information provides a more robust estimate of ENSO variance than synthesizing the raw data and then identifying its running variance. We also examine whether good temporal correspondence between proxy data and instrumental ENSO records implies a good representation of ENSO variance. In the climate modeling framework we show that a significant improvement in reconstructing ENSO variance changes is found when combining information from diverse ENSO-teleconnected source regions, rather than by relying on a single well-correlated location. This suggests that ENSO variance estimates derived from a single site should be viewed with caution. Finally, synthesizing existing ENSO reconstructions to arrive at a better estimate of past ENSO variance changes, we find robust evidence that the ENSO variance for any 30 yr period during the interval 1590–1880 was considerably lower than that observed during 1979–2009

Extensive Chaos in the Nikolaevskii Model

We carry out a systematic study of a novel type of chaos at onset ("soft-mode turbulence") based on numerical integration of the simplest one dimensional model. The chaos is characterized by a smooth interplay of different spatial scales, with defect generation being unimportant. The Lyapunov exponents are calculated for several system sizes for fixed values of the control parameter $\epsilon$. The Lyapunov dimension and the Kolmogorov-Sinai entropy are calculated and both shown to exhibit extensive and microextensive scaling. The distribution functional is shown to satisfy Gaussian statistics at small wavenumbers and small frequency.Comment: 4 pages (including 5 figures) LaTeX file. Submitted to Phys. Rev. Let

Parameter estimation in spatially extended systems: The Karhunen-Loeve and Galerkin multiple shooting approach

Parameter estimation for spatiotemporal dynamics for coupled map lattices and continuous time domain systems is shown using a combination of multiple shooting, Karhunen-Loeve decomposition and Galerkin's projection methodologies. The resulting advantages in estimating parameters have been studied and discussed for chaotic and turbulent dynamics using small amounts of data from subsystems, availability of only scalar and noisy time series data, effects of space-time parameter variations, and in the presence of multiple time-scales.Comment: 11 pages, 5 figures, 4 Tables Corresponding Author - V. Ravi Kumar, e-mail address: [email protected]

Eccrine porocarcinoma of the head: An important differential diagnosis in the elderly patient

Background: Eccrine porocarcinoma is a rare malignant tumor of the sweat gland, characterized by a broad spectrum of clinicopathologic presentations. Surprisingly, unlike its benign counterpart eccrine poroma, eccrine porocarcinoma is seldom found in areas with a high density of eccrine sweat glands, like the palms or soles. Instead, eccrine porocarcinoma frequently occurs on the lower extremities, trunk and abdomen, but also on the head, resembling various other skin tumors, as illustrated in the patients described herein. Observations: We report 5 cases of eccrine porocarcinoma of the head. All patients were initially diagnosed as having epidermal or melanocytic skin tumors. Only after histopathologic examination were they classified as eccrine porocarcinoma, showing features of epithelial tumors with abortive ductal differentiation. Characteristic clinical, histopathologic and immunohistochemical findings of eccrine porocarcinomas are illustrated. Conclusion: Eccrine porocarcinomas are potentially fatal adnexal malignancies, in which extensive metastatic dissemination may occur. Porocarcinomas are commonly overlooked, or misinterpreted as squamous or basal cell carcinomas as well as other common malignant and even benign skin tumors. Knowledge of the clinical pattern and histologic findings, therefore, is crucial for an early therapeutic intervention, which can reduce the risk of tumor recurrence and serious complications. Copyright (c) 2008 S. Karger AG, Basel

Metastability in pressure-induced structural transformations of CdSe/ZnS core/shell nanocrystals

The kinetics and thermodynamics of structural transformations under pressure depend strongly on particle size due to the influence of surface free energy. By suitable design of surface structure, composition, and passivation it is possible, in principle, to prepare nanocrystals in structures inaccessible to bulk materials. However, few realizations of such extreme size-dependent behavior exist. Here we show with molecular dynamics computer simulation that in a model of CdSe/ZnS core/shell nanocrystals the core high pressure structure can be made metastable under ambient conditions by tuning the thickness of the shell. In nanocrystals with thick shells, we furthermore observe a wurtzite to NiAs transformation, which does not occur in the pure bulk materials. These phenomena are linked to a fundamental change in the atomistic transformation mechanism from heterogenous nucleation at the surface to homogenous nucleation in the crystal core. Our results suggest a new route towards expanding the range of available nanoscale materials

Resource utilisation and costs in predementia and dementia: a systematic review protocol

Introduction Dementia is the fastest growing major cause of disability globally with a mounting social and financial impact for patients and their families but also to health and social care systems. This review aims to systematically synthesise evidence on the utilisation of resources and costs incurred by patients and their caregivers and by health and social care services across the full spectrum of dementia, from its preceding preclinical stage to end of life. The main drivers of resources used and costs will also be identified. Methods and analysis A systematic literature review was conducted in MEDLINE, EMBASE, CDSR, CENTRAL, DARE, EconLit, CEA Registry, TRIP, NHS EED, SCI, RePEc and OpenGrey between January 2000 and beginning of May 2017. Two reviewers will independently assess each study for inclusion and disagreements will be resolved by a third reviewer. Data will be extracted using a predefined data extraction form following best practice. Study quality will be assessed with the Effective Public Health Practice Project quality assessment tool. The reporting of costing methodology will be assessed using the British Medical Journal checklist. A narrative synthesis of all studies will be presented for resources used and costs incurred, by level of disease severity when available. If feasible, the data will be synthesised using appropriate statistical techniques. Ethics and dissemination Included articles will be reviewed for an ethics statement. The findings of the review will be disseminated in a related peer-reviewed journal and presented at conferences. They will also contribute to the work developed in the Real World Outcomes across the Alzheimer’s disease spectrum for better care: multi-modal data access platform (ROADMAP)