A monte carlo approach to population dynamics of cells in a HIV immune response model

Summary Using a direct Monte Carlo simulation, population growth of helper T-cells (N _H) and viral cells (N _v) is studied for an immune response model with an enhanced spatial inter-cellular interaction relevant to HIV as a function of viral mutation. In the absence of cellular mobility (P _mob=0), the helper T-cells grow nonmonotonically before reaching saturation and the viral population grows monotonically before reaching a constant equilibrium. Cellular mobility (P _mob=1) enhances the viral growth and reduces the stimulative T-cell growth. Below a mutation threshold (P _c), the steady-state density of helper T-cell (p _H) is larger than that of the Virus (p _v); the density difference Δp _o(=pV−pH) remains a constant at P _mob=1 while −Δp _o→0 as P _mut→P _c at P _mob=0. Above the mutation threshold, the difference Δp _o in cell density, grows with ΔP=P _mut−P _c monotonically: ΔP _o ∞ (ΔP)^β ≃ with β≈0.574±0.016 in absence of mobility, while Δp _o≈6(ΔP) with P _mob=1.     

Effect of mutation on helper T-cells and viral population: A computer simulation model for HIV

Summary A Monte Carlo simulation is proposed to study the dynamics of helper T-cells (N _H) and viral (N _V) populations in an immune response model relevant to HIV. Cellular states are binary variables and the interactions are described by logical expressions. Viral population shows a nonmonotonic growth before reaching a constant value while helper T-cells grow to a constant after a relaxation/reaction time. Initially, the population of helper cells grows with time with a power-law, N _H ∼t ^β, before reaching the steady-state; the growth exponent β increases systematically (β ≈ 1 – 2) with the mutation rate (P _mut≈0.1–0.4). The critical recovery time (t _c) increases exponentially with the viral mutation, t _c≈Ae ^αP _mut , with α=4.52±0.29 in low mutation regime and α=15.21±1.41 in high mutation regime. The equilibrium population of helper T-cell declines slowly with P _mut and collapses at ∼ 0.40; the viral population exhibits a reverse trend, i.e., a slow increase before the burst around the same mutation regime.     

Ecosystem Responses to Nitrogen Deposition in the Colorado Front Range

We asked whether 3–5 kg N y⁻¹ atmospheric N deposition was sufficient to have influenced natural, otherwise undisturbed, terrestrial and aquatic ecosystems of the Colorado Front Range by comparing ecosystem processes and properties east and west of the Continental Divide. The eastern side receives elevated N deposition from urban, agricultural, and industrial sources, compared with 1–2 kg N y⁻¹ on the western side. Foliage of east side old-growth Englemann spruce forests have significantly lower C:N and lignin:N ratios and greater N:Mg and N:P ratios. Soil % N is higher, and C:N ratios lower in the east side stands, and potential net N mineralization rates are greater. Lake NO₃ concentrations are significantly higher in eastern lakes than western lakes. Two east side lakes studied paleolimnologically revealed rapid changes in diatom community composition and increased biovolumes and cell concentrations. The diatom flora is now representative of increased disturbance or eutrophication. Sediment nitrogen isotopic ratios have become progressively lighter over the past 50 years, coincident with the change in algal flora, possibly from an influx of isotopically light N volatilized from agricultural fields and feedlots. Seventy-five percent of the increased east side soil N pool can be accounted for by increased N deposition commensurate with human settlement. Nitrogen emissions from fixed, mobile, and agricultural sources have increased dramatically since approximately 1950 to the east of the Colorado Front Range, as they have in many parts of the world. Our findings indicate even slight increases in atmospheric deposition lead to measurable changes in ecosystem properties. Received 16 November 1999; accepted 8 February 2000.     

Modification of an algal culture medium for sustained growth of a saxitoxin-producing isolate of Alexandrium minutum

In order to study saxitoxin (STX) production bymicro-algae in the laboratory, a defined algal culture medium which supports optimum growth over a longtime-period is a requirement. In the development of such a medium, a number of modifications were made to a standard algal culture medium (GP) and growth of a STX-producing isolate of Alexandrium minutum in the different formulations was assessed by measuring maximum cell densities and mean generation times (MGT). All experiments were carried out under controlled conditions in an aerobic atmosphere with increased CO₂. Whilst maximum cell densities in the different modifications were similar, the MGT was significantly shortened by the addition of Tris buffer and the trace metals strontium, selenium and molybdenum. Replacement of natural with artificial seawater and removal of soil extract did not adversely affect algal growth. Five of the six media formulations supported the growth of A. minutumover a 9-month period. This revised version was published online in August 2006 with corrections to the Cover Date.     

Ten simple rules to host an inclusive conference

Conferences are spaces to meet and network within and across academic and technical fields, learn about new advances, and share our work. They can help define career paths and create long-lasting collaborations and opportunities. However, these opportunities are not equal for all. This article introduces 10 simple rules to host an inclusive conference based on the authors’ recent experience organizing the 2021 edition of the useR! statistical computing conference, which attracted a broad range of participants from academia, industry, government, and the nonprofit sector. Coming from different backgrounds, career stages, and even continents, we embraced the challenge of organizing a high-quality virtual conference in the context of the Coronavirus Disease 2019 (COVID-19) pandemic and making it a kind, inclusive, and accessible experience for as many people as possible. The rules result from our lessons learned before, during, and after the organization of the conference. They have been written mainly for potential organizers and selection committees of conferences and contain multiple practical tips to help a variety of events become more accessible and inclusive. We see this as a starting point for conversations and efforts towards building more inclusive conferences across the world. * Translated versions of the English abstract and the list of rules are available in 10 languages in S1 Text: Arabic, French, German, Italian, Japanese, Korean, Portuguese, Spanish, Tamil, and Thai.     

Genome-Wide Association Studies in an Isolated Founder Population from the Pacific Island of Kosrae

It has been argued that the limited genetic diversity and reduced allelic heterogeneity observed in isolated founder populations facilitates discovery of loci contributing to both Mendelian and complex disease. A strong founder effect, severe isolation, and substantial inbreeding have dramatically reduced genetic diversity in natives from the island of Kosrae, Federated States of Micronesia, who exhibit a high prevalence of obesity and other metabolic disorders. We hypothesized that genetic drift and possibly natural selection on Kosrae might have increased the frequency of previously rare genetic variants with relatively large effects, making these alleles readily detectable in genome-wide association analysis. However, mapping in large, inbred cohorts introduces analytic challenges, as extensive relatedness between subjects violates the assumptions of independence upon which traditional association test statistics are based. We performed genome-wide association analysis for 15 quantitative traits in 2,906 members of the Kosrae population, using novel approaches to manage the extreme relatedness in the sample. As positive controls, we observe association to known loci for plasma cholesterol, triglycerides, and C-reactive protein and to a compelling candidate loci for thyroid stimulating hormone and fasting plasma glucose. We show that our study is well powered to detect common alleles explaining ≥5% phenotypic variance. However, no such large effects were observed with genome-wide significance, arguing that even in such a severely inbred population, common alleles typically have modest effects. Finally, we show that a majority of common variants discovered in Caucasians have indistinguishable effect sizes on Kosrae, despite the major differences in population genetics and environment.     

Insights into the feeding ecology of the Seychelles Black Parrot Coracopsis barklyi using two monitoring approaches

Feeding ecology is an important factor for the survival of a species and knowledge of its parameters is a prerequisite for successful conservation work. In this study we describe the feeding ecology of the endemic Seychelles Black Parrot Coracopsis barklyi on Praslin, Seychelles, the only island on which this parrot is resident. We compared two methods to evaluate feeding choices: incidental observations and feeding walks on 25 transects in all habitat types. Black parrots fed on 46 different species, bringing the total number of known food plants to 53 species. They predominantly consumed endemic and native species (58% of observed feeding bouts), mainly their fruit pulp (in 68% of feeding bouts), followed by buds (15%) and seeds (37%) with occasional observations of leaves, bark and scale insects. The incidental method rendered many more observed bouts than the transect approach and the ratios of consumed species differed between methods but the transect results are regarded as more representative. The incidental method is not suitable for quantitative conclusions but complements the transect method, providing information about rarely occurring feeding events.     

The influence of cultivation methods on Shewanella oneidensis physiology and proteome expression

High-throughput analyses that are central to microbial systems biology and ecophysiology research benefit from highly homogeneous and physiologically well-defined cell cultures. While attention has focused on the technical variation associated with high-throughput technologies, biological variation introduced as a function of cell cultivation methods has been largely overlooked. This study evaluated the impact of cultivation methods, controlled batch or continuous culture in bioreactors versus shake flasks, on the reproducibility of global proteome measurements in Shewanella oneidensis MR-1. Variability in dissolved oxygen concentration and consumption rate, metabolite profiles, and proteome was greater in shake flask than controlled batch or chemostat cultures. Proteins indicative of suboxic and anaerobic growth (e.g., fumarate reductase and decaheme c-type cytochromes) were more abundant in cells from shake flasks compared to bioreactor cultures, a finding consistent with data demonstrating that “aerobic” flask cultures were O₂ deficient due to poor mass transfer kinetics. The work described herein establishes the necessity of controlled cultivation for ensuring highly reproducible and homogenous microbial cultures. By decreasing cell to cell variability, higher quality samples will allow for the interpretive accuracy necessary for drawing conclusions relevant to microbial systems biology research.     

Hexasaccharides from the histamine-modified depolymerization of porcine intestinal mucosal heparin

Specific sequences in heparin are responsible for its modulation of the biological activity of proteins. As part of a program to characterize heparin-peptide and heparin-protein binding, we are studying the interaction of chemically discrete heparin-derived oligosaccharides with peptides and proteins. We report here the isolation and characterization, by one- and two-dimensional 1H NMR spectroscopies, of ten hexasaccharides, one pentasaccharide, and one octasaccharide serine that were isolated from depolymerized porcine intestinal mucosal heparin. Hexasaccharides were chosen for study because they fall within the size range, typically tetra- to decasaccharide in length, of heparin sequences that modulate the activity of proteins. The depolymerization reaction was catalyzed by heparinase I (EC 4.2.2.7) in the presence of histamine, which binds site specifically to heparin. Histamine increases both the rate and extent of heparinase I-catalyzed depolymerization of heparin. It is proposed that oligosaccharides produced by heparinase I-catalyzed depolymerization can inhibit the enzyme by binding to the imidazolium group of histidine-203, which together with cysteine-135 forms the catalytic domain of heparinase I. The increased rate and extent of depolymerization are attributed to competitive binding of the oligosaccharides by histamine.