Exploiting sparseness in de novo genome assembly

Background: The very large memory requirements for the construction of assembly graphs for de novo genome assembly limit current algorithms to super-computing environments. Methods: In this paper, we demonstrate that constructing a sparse assembly graph which stores only a small fraction of the observed k- mers as nodes and the links between these nodes allows the de novo assembly of even moderately-sized genomes (~500 M) on a typical laptop computer. Results: We implement this sparse graph concept in a proof-of-principle software package, SparseAssembler, utilizing a new sparse k- mer graph structure evolved from the de Bruijn graph. We test our SparseAssembler with both simulated and real data, achieving ~90% memory savings and retaining high assembly accuracy, without sacrificing speed in comparison to existing de novo assemblers

CARMA1 is a novel regulator of T-ALL disease and leukemic cell migration to the CNS

No abstract available

Using ensemble-mean climate scenarios for future crop yield projections: a stochastic weather generator

Using climate scenarios from only 1 or a small number of global climate models (GCMs) in climate change impact studies may lead to biased assessment due to large uncertainty in climate projections. Ensemble means in impact projections derived from a multi-GCM ensemble are often used as best estimates to reduce bias. However, it is often time consuming to run process-based models (e.g. hydrological and crop models) in climate change impact studies using numerous climate scenarios. It would be interesting to investigate if using a reduced number of climate scenarios could lead to a reasonable estimate of the ensemble mean. In this study, we generated a single ensemble-mean climate scenario (En-WG scenario) using ensemble means of the change factors derived from 20 GCMs included in CMIP5 to perturb the parameters in a weather generator, LARS-WG, for selected locations across Canada. We used En-WG scenarios to drive crop growth models in DSSAT ver. 4.7 to simulate crop yields for canola and spring wheat under RCP4.5 and RCP8.5 emission scenarios. We evaluated the potential of using the En-WG scenario to simulate crop yields by comparing them with crop yields simulated with the LARS-WG generated climate scenarios based on each of the 20 GCMs (WG scenarios). Our results showed that simulated crop yields using the En-WG scenarios were often close to the ensemble means of simulated crop yields using the 20 WG scenarios with a high probability of outperforming simulations based on a randomly selected GCM. Further studies are required, as the results of the proposed approach may be influenced by selected crop types, crop models, weather generators, and GCM ensembles

Effectiveness of using representative subsets of global climate models in future crop yield projections.

Representative subsets of global climate models (GCMs) are often used in climate change impact studies to account for uncertainty in ensemble climate projections. However, the effectiveness of such subsets has seldom been assessed for the estimations of either the mean or the spread of the full ensembles. We assessed two different approaches that were employed to select 5 GCMs from a 20-member ensemble of GCMs from the CMIP5 ensemble for projecting canola and spring wheat yields across Canada under RCP 4.5 and 8.5 emission scenarios in the periods 2040-2069 and 2070-2099, based on crop simulation models. Averages and spreads of the simulated crop yields using the 5-GCM subsets selected by T&P and KKZ approaches were compared with the full 20-GCM ensemble. Our results showed that the 5-GCM subsets selected by the two approaches could produce full-ensemble means with a relative absolute error of 2.9 – 4.7% for canola and 1.5 – 2.2% for spring wheat, and covers 61.8 – 91.1% and 66.1 – 80.8% of the full-ensemble spread for canola and spring wheat, respectively. Our results also demonstrated that both approaches were very likely to outperform a subset of randomly selected 5 GCMs in terms of a smaller error and a larger range

A mechanical bottleneck explains the variation in cup growth during FcγR phagocytosis

Phagocytosis is the process by which cells internalize particulate material, and is of central importance to immunity, homeostasis and development. Here, we study the internalization of immunoglobulin G-coated particles in cells transfected with Fcγ receptors (FcγRs) through the formation of an enveloping phagocytic cup. Using confocal microscopy, we precisely track the location of fluorescently tagged FcγRs during cup growth. Surprisingly, we found that phagocytic cups growing around identical spherical particles showed great variability even within a single cell and exhibited two eventual fates: a cup either stalled before forming a half-cup or it proceeded until the particle was fully enveloped. We explain these observations in terms of a mechanical bottleneck using a simple mathematical model of the overall process of cup growth. The model predicts that reducing F-actin concentration levels, and hence the deforming force, does not necessarily lead to stalled cups, a prediction we verify experimentally. Our analysis gives a coherent explanation for the importance of geometry in phagocytic uptake and provides a unifying framework for integrating the key processes, both biochemical and mechanical, occurring during cup growth

Etoricoxib-induced life-threatening hyperkalemia and acute kidney dysfunction against the background of telmisartan and a low sodium diet

Drug-induced hyperkalemia is not uncommon and may be life-threatening when presenting acutely in the emergency department. We present a case of severe hyperkalemia precipitated acutely by etoricoxib in a patient who was on telmisartan and a low sodium (potassium chloride-rich) diet. A 75-year-old male with a past medical history of well-controlled diabetes and hypertension was prescribed etoricoxib (90 mg daily) for 3 days for musculoskeletal backache. He had been taking his routine medications including telmisartan and a potassium-rich salt substitute for many years, without any recent change in dosage or quantity. There was evidence of microalbuminurea; however, the renal functions and electrolytes prior to starting etoricoxib were normal. He presented to the emergency department with signs and symptoms of life-threatening hyperkalemia (serum potassium 7.7 mEq/dl), accelerated hypertension, congestive heart failure, pulmonary edema and acute renal failure. Acute medical management and withholding all drugs that could cause hyperkalemia improved his serum potassium levels over 24 h and renal parameters within 5 days. All the other drugs except etoricoxib were restarted under observation over 8 weeks with no recurrence of the acute episode. Non-steroidal analgesics and other COX-2 inhibitors (rofecoxib and celecoxib) have been known to precipitate renal failure and hyperkalemia specially in patients at risk for the same; although not unexpected, this may be the first reported case of life-threatening hyperkalemia precipitated by etoricoxib in a previously stable patient having increased risk of renal failure and hyperkalemia

Fibril elongation mechanisms of HET-s prion-forming domain: Topological evidence for growth polarity

The prion-forming C-terminal domain of the fungal prion HET-s forms infectious amyloid fibrils at physiological pH. The conformational switch from the non-prion soluble form to the prion fibrillar form is believed to have a functional role, since HET-s in its prion form participates in a recognition process of different fungal strains. Based on the knowledge of the high-resolution structure of HET-s(218-289) (the prion forming-domain) in its fibrillar form, we here present a numerical simulation of the fibril growth process which emphasizes the role of the topological properties of the fibrillar structure. An accurate thermodynamic analysis of the way an intervening HET-s chain is recruited to the tip of the growing fibril suggests that elongation proceeds through a dock and lock mechanism. First, the chain docks onto the fibril by forming the longest $\beta$-strands. Then, the re-arrangement in the fibrillar form of all the rest of molecule takes place. Interestingly, we predict also that one side of the HET-s fibril is more suitable for substaining its growth with respect to the other. The resulting strong polarity of fibril growth is a consequence of the complex topology of HET-s fibrillar structure, since the central loop of the intervening chain plays a crucially different role in favouring or not the attachment of the C-terminus tail to the fibril, depending on the growth side.Comment: 16 pages, 10 figure