Abstract
With the desire to model population genetic processes under increasingly realistic scenarios, forward genetic simulations have become a critical part of the toolbox of modern evolutionary ...biology. The SLiM forward genetic simulation framework is one of the most powerful and widely used tools in this area. However, its foundation in the Wright–Fisher model has been found to pose an obstacle to implementing many types of models; it is difficult to adapt the Wright–Fisher model, with its many assumptions, to modeling ecologically realistic scenarios such as explicit space, overlapping generations, individual variation in reproduction, density-dependent population regulation, individual variation in dispersal or migration, local extinction and recolonization, mating between subpopulations, age structure, fitness-based survival and hard selection, emergent sex ratios, and so forth. In response to this need, we here introduce SLiM 3, which contains two key advancements aimed at abolishing these limitations. First, the new non-Wright–Fisher or “nonWF” model type provides a much more flexible foundation that allows the easy implementation of all of the above scenarios and many more. Second, SLiM 3 adds support for continuous space, including spatial interactions and spatial maps of environmental variables. We provide a conceptual overview of these new features, and present several example models to illustrate their use.
Ten simple rules for reporting a bug Haller, Benjamin C
PLOS computational biology/PLoS computational biology,
10/2022, Volume:
18, Issue:
10
Journal Article
Peer reviewed
Open access
A good way to pretty much guarantee that the bug you’re reporting will not get fixed promptly, if at all, is to attack the developer; the developer, understandably, will not feel much interest in ...helping you in return (although your bug might get fixed anyway if it’s critical—causing incorrect results to be produced, for example). ...keep in mind that people go on vacation, many people don’t check their email at all on weekends, and so forth. Open source software, such as software on GitHub, usually has a public issue database where you can look up bugs. First of all, which button?
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
3.
Remote sensing of the nearshore Holman, Rob; Haller, Merrick C
Annual review of marine science,
01/2013, Volume:
5
Journal Article
Peer reviewed
The shallow waters of the nearshore ocean are popular, dynamic, and often hostile. Prediction in this domain is usually limited less by our understanding of the physics or by the power of our models ...than by the availability of input data, such as bathymetry and wave conditions. It is a challenge for traditional in situ instruments to provide these inputs with the appropriate temporal or spatial density or at reasonable logistical or financial costs. Remote sensing provides an attractive alternative. We discuss the range of different sensors that are available and the differing physical manifestations of their interactions with the ocean surface. We then present existing algorithms by which the most important geophysical variables can be estimated from remote sensing measurements. Future directions and opportunities will depend on expected developments in sensors and platforms and on improving processing algorithms, including data assimilation formalisms.
Background
Steroid‐sparing strategies have been attempted in recent decades to avoid morbidity from long‐term steroid intake among kidney transplant recipients. Previous systematic reviews of steroid ...withdrawal after kidney transplantation have shown a significant increase in acute rejection. There are various protocols to withdraw steroids after kidney transplantation and their possible benefits or harms are subject to systematic review. This is an update of a review first published in 2009.
Objectives
To evaluate the benefits and harms of steroid withdrawal or avoidance for kidney transplant recipients.
Search methods
We searched the Cochrane Kidney and Transplant Specialised Register to 15 February 2016 through contact with the Information Specialist using search terms relevant to this review.
Selection criteria
All randomised and quasi‐randomised controlled trials (RCTs) in which steroids were avoided or withdrawn at any time point after kidney transplantation were included.
Data collection and analysis
Assessment of risk of bias and data extraction was performed by two authors independently and disagreement resolved by discussion. Statistical analyses were performed using the random‐effects model and dichotomous outcomes were reported as relative risk (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals.
Main results
We included 48 studies (224 reports) that involved 7803 randomised participants. Of these, three studies were conducted in children (346 participants). The 2009 review included 30 studies (94 reports, 5949 participants). Risk of bias was assessed as low for sequence generation in 19 studies and allocation concealment in 14 studies. Incomplete outcome data were adequately addressed in 22 studies and 37 were free of selective reporting.
The 48 included studies evaluated three different comparisons: steroid avoidance or withdrawal compared with steroid maintenance, and steroid avoidance compared with steroid withdrawal. For the adult studies there was no significant difference in patient mortality either in studies comparing steroid withdrawal versus steroid maintenance (10 studies, 1913 participants, death at one year post transplantation: RR 0.68, 95% CI 0.36 to 1.30) or in studies comparing steroid avoidance versus steroid maintenance (10 studies, 1462 participants, death at one year after transplantation: RR 0.96, 95% CI 0.52 to 1.80). Similarly no significant difference in graft loss was found comparing steroid withdrawal versus steroid maintenance (8 studies, 1817 participants, graft loss excluding death with functioning graft at one year after transplantation: RR 1.17, 95% CI 0.72 to 1.92) and comparing steroid avoidance versus steroid maintenance (7 studies, 1211 participants, graft loss excluding death with functioning graft at one year after transplantation: RR 1.09, 95% CI 0.64 to 1.86). The risk of acute rejection significantly increased in patients treated with steroids for less than 14 days after transplantation (7 studies, 835 participants: RR 1.58, 95% CI 1.08 to 2.30) and in patients who were withdrawn from steroids at a later time point after transplantation (10 studies, 1913 participants, RR 1.77, 95% CI 1.20 to 2.61). There was no evidence to suggest a difference in harmful events, such as infection and malignancy, in adult kidney transplant recipients. The effect of steroid withdrawal in children is unclear.
Authors' conclusions
This updated review increases the evidence that steroid avoidance and withdrawal after kidney transplantation significantly increase the risk of acute rejection. There was no evidence to suggest a difference in patient mortality or graft loss up to five year after transplantation, but long‐term consequences of steroid avoidance and withdrawal remain unclear until today, because prospective long‐term studies have not been conducted.
Recent studies demonstrated that the performance of InGaN/GaN quantum well (QW) light emitting diodes (LEDs) can be significantly improved through the insertion of an InGaN underlayer (UL). The ...current working hypothesis is that the presence of the UL reduces the density of non-radiative recombination centers (NRCs) in the QW itself: during the growth of the UL, surface defects are effectively buried in the UL, without propagating towards the QW region. Despite the importance of this hypothesis, the concentration profile of defects in the quantum wells of LEDs with and without the UL was never investigated in detail. This paper uses combined capacitance-voltage and steady-state photocapacitance measurements to experimentally identify the defects acting as NRCs and to extract a depth-profile of the traps, thus proving the incorporation upon indium-reaction. Specifically: (i) we demonstrate that LEDs without UL have a high density (9.2 × 1015 cm−3) of defects, compared to samples with UL (0.8 × 1015 cm−3); (ii) defects are located near midgap (EC-1.8 eV, corresponding to Ei-ET ∼ 0.3 eV), thus acting as efficient NRCs; (iii) crucially, the density of defects has a peak within the QWs, indicating that traps are segregated at the first grown InGaN layers; (iv) we propose a model to calculate trap distribution in the QW, and we demonstrate a good correspondence with experimental data. These results provide unambiguous demonstration of the role of UL in limiting the propagation of defects towards the QWs, and the first experimental characterization of the properties of the related traps.
ABSTRACT
Background
Calciprotein particles (CPPs), colloidal mineral-protein nanoparticles, have emerged as potential mediators of phosphate toxicity in dialysis patients, with putative links to ...vascular calcification, endothelial dysfunction and inflammation. We hypothesized that phosphate binder therapy with sucroferric oxyhydroxide (SO) would reduce endogenous CPP levels and attenuate pro-calcific and pro-inflammatory effects of patient serum towards human vascular cells in vitro.
Methods
This secondary analysis of a randomised controlled crossover study compared the effect of 2-week phosphate binder washout with high-dose (2000 mg/day) and low-dose (250 mg/day) SO therapy in 28 haemodialysis patients on serum CPP levels, inflammatory cytokine/chemokine arrays and human aortic smooth muscle cell (HASMC) and coronary artery endothelial cell (HCAEC) bioassays.
Results
In our cohort (75% male, 62 ± 12 years) high-dose SO reduced primary (amorphous) and secondary (crystalline) CPP levels {−62% 95% confidence interval (CI) −76 to −44, P < .0001 and −38% −62 to −0.14, P < .001, respectively} compared with washout. Nine of 14 plasma cytokines/chemokines significantly decreased with high-dose SO, with consistent reductions in interleukin-6 (IL-6) and IL-8. Exposure of HASMC and HCAEC cultures to serum of SO-treated patients reduced calcification and markers of activation (IL-6, IL-8 and vascular cell adhesion protein 1) compared with washout. Serum-induced HASMC calcification and HCAEC activation was ameliorated by removal of the CPP-containing fraction from patient sera. Effects of CPP removal were confirmed in an independent cohort of chronic kidney disease patients.
Conclusions
High-dose SO reduced endogenous CPP formation in dialysis patients and yielded serum with attenuated pro-calcific and inflammatory effects in vitro.
Graphical Abstract
Graphical Abstract
Summary
Iron is an essential element for almost all organisms, although an overload of this element results in toxicity because of the formation of hydroxyl radicals. Consequently, most living ...entities have developed sophisticated mechanisms to control their intracellular iron concentration. In many bacteria, including the opportunistic pathogen Pseudomonas aeruginosa, this task is performed by the ferric uptake regulator (Fur). Fur controls a wide variety of basic physiological processes including iron uptake systems and the expression of exotoxin A. Here, we present the first crystal structure of Fur from P. aeruginosa in complex with Zn2+ determined at a resolution of 1.8 Å. Furthermore, X‐ray absorption spectroscopic measurements and microPIXE analysis were performed in order to characterize the distinct zinc and iron binding sites in solution. The combination of these complementary techniques enables us to present a model for the activation and DNA binding of the Fur protein.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We identify two processes by which humans increase genetic exchange among groups of individuals: by affecting the distribution of groups and dispersal patterns across a landscape, and by affecting ...interbreeding among sympatric or parapatric groups. Each of these processes might then have two different effects on biodiversity: changes in the number of taxa through merging or splitting of groups, and the extinction/extirpation of taxa through effects on fitness. We review the various ways in which humans are affecting genetic exchange, and highlight the difficulties in predicting the impacts on biodiversity. Gene flow and hybridization are crucially important evolutionary forces influencing biodiversity. Humans alter natural patterns of genetic exchange in myriad ways, and these anthropogenic effects are likely to influence the genetic integrity of populations and species. We argue that taking a gene‐centric view towards conservation will help resolve issues pertaining to conservation and management.
Editor's suggested further reading in BioEssays A systemic view of biodiversity and its conservation: Processes, interrelationships, and human culture
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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