Charting a new frontier of science by integrating mathematical modeling to understand and predict complex biological systems

Biological systems are staggeringly complex. To untangle this complexity and make predictions about biological systems is a continuous goal of biological research. One approach to achieve these goals is to emphasize the use of quantitative measures of biological processes. Advances in quantitative biology data collection and analysis across scales (molecular, cellular, organismal, ecological) has transformed how we understand, categorize, and predict complex biological systems. Simultaneously, thanks to increased computational power, mathematicians, engineers and physical scientists -- collectively termed theoreticians -- have developed sophisticated models of biological systems at different scales. But there is still a disconnect between the two fields. This surge of quantitative data creates an opportunity to apply, develop, and evaluate mathematical models of biological systems and explore novel methods of analysis. The novel modeling schemes can also offer deeper understanding of principles in biology. In the context of this paper, we use “models” to refer to mathematical representations of biological systems. This data revolution puts scientists in a unique position to leverage information-rich datasets to improve descriptive modeling. Moreover, advances in technology allow inclusion of heterogeneity and variability within these datasets and mathematical models. This inclusion may lead to identifying previously undetermined variables driving or maintaining heterogeneity and diversity. Improved inclusion of variation may even improve biologically meaningful predictions about how systems will respond to perturbations. Although some of these practices are mainstream in specific sub-fields of biology, such practices are not widespread across all fields of biological sciences. With resources dedicated to better integrating biology and mathematical modeling, we envision a transformational improvement in the ability to describe and predict complex biological systems

Three-Dimensional Simulations of Magnetized Superbubbles: New Insights into the Importance of MHD Effects on Observed Quantities

We present three-dimensional magnetohydrodynamic (MHD) simulations of superbubbles, to study the importance of MHD effects in the interpretation of images from recent surveys of the Galactic plane. These simulations focus mainly on atmospheres defined by an exponential density distribution and the Dickey & Lockman (1990) density distribution. In each case, the magnetic field is parallel to the Galactic plane and we investigate cases with either infinite scale height (constant magnetic field) or a constant ratio of gas pressure to magnetic pressure. The three-dimensional structure of superbubbles in these simulations is discussed with emphasis on the axial ratio of the cavity as a function of magnetic field strength and the age of the bubble. We investigate systematic errors in the age of the bubble and scale height of the surrounding medium that may be introduced by modeling the data with purely hydrodynamic models. Age estimates derived with symmetric hydrodynamic models fitted to an asymmetric magnetized superbubble can differ by up to a factor of four, depending on the direction of the line of sight. The scale height of the surrounding medium based on the Kompaneets model may be up to 50% lower than the actual scale height. We also present the first ever predictions of Faraday rotation by a magnetized superbubble based on three-dimensional MHD simulations. We emphasize the importance of MHD effects in the interpretation of observations of superbubbles.Comment: 21 journal pages. 17 figures. 5 tables (added extensive discussion on the effect of cooling on the bubbles); Accepted for publications in the Astrophysical Journal. Related animations can be accessed via http://www.capca.ucalgary.c

Fin whales of the Great Bear Rainforest : Balaenoptera physalus velifera in a Canadian Pacific fjord system

Funding: This research was supported by a Mitacs Accelerate Internship (IT21479); the Save Our Seas Foundation; Willow Grove Foundation; Donner Canadian Foundation; Tides Canada; LUSH Charity Pot; private donations to North Coast Cetacean Society; Fisheries and Oceans Canada; and the Canada Nature Fund for Aquatic Species at Risk (CANAFSAR 2019-2021).Fin whales (Balaenoptera physalus) are widely considered an offshore and oceanic species, but certain populations also use coastal areas and semi-enclosed seas. Based upon fifteen years of study, we report that Canadian Pacific fin whales (B. p. velifera) have returned to the Kitimat Fjord System (KFS) in the Great Bear Rainforest, and have established a seasonally resident population in its intracoastal waters. This is the only fjord system along this coast or elsewhere in which fin whales are known to occur regularly with strong site fidelity. The KFS was also the only Canadian Pacific fjord system in which fin whales were commonly found and killed during commercial whaling, pointing to its long-term importance. Traditional knowledge, whaling records, and citizen science databases suggest that fin whales were extirpated from this area prior to their return in 2005-2006. Visual surveys and mark-recapture analysis documented their repopulation of the area, with 100-120 whales using the fjord system in recent years, as well as the establishment of a seasonally resident population with annual return rates higher than 70%. Line transect surveys identified the central and outer channels of the KFS as the primary fin whale habitat, with the greatest densities occurring in Squally Channel and Caamano Sound. Fin whales were observed in the KFS in most months of the year. Vessel- and shore-based surveys (27,311 km and 6,572 hours of effort, respectively) indicated regular fin whale presence (2,542 detections), including mother-calf pairs, from June to October and peak abundance in late August-early September. Seasonal patterns were variable year-to-year, and several lines of evidence indicated that fin whales arrived and departed from the KFS repeatedly throughout the summer and fall. Additionally, we report on the population's social network and morphometrics. These findings offer insights into the dynamics of population recovery in an area where several marine shipping projects are proposed. The fin whales of the Great Bear Rainforest represent a rare exception to general patterns in this species' natural history, and we highlight the importance of their conservation.Publisher PDFPeer reviewe

Organic Wastes Amended with Sorbents Reduce N2O Emissions from Sugarcane Cropping

Nutrient-rich organic wastes and soil ameliorants can benefit crop performance and soil health but can also prevent crop nutrient sufficiency or increase greenhouse gas emissions. We hypothesised that nitrogen (N)-rich agricultural waste (poultry litter) amended with sorbents (bentonite clay or biochar) or compost (high C/N ratio) attenuates the concentration of inorganic nitrogen (N) in soil and reduces emissions of nitrous oxide (N2O). We tested this hypothesis with a field experiment conducted on a commercial sugarcane farm, using in vitro incubations. Treatments received 160 kg N ha−1, either from mineral fertiliser or poultry litter, with additional N (2–60 kg N ha−1) supplied by the sorbents and compost. Crop yield was similar in all N treatments, indicating N sufficiency, with the poultry litter + biochar treatment statistically matching the yield of the no-N control. Confirming our hypothesis, mineral N fertiliser resulted in the highest concentrations of soil inorganic N, followed by poultry litter and the amended poultry formulations. Reflecting the soil inorganic N concentrations, the average N2O emission factors ranked as per the following: mineral fertiliser 8.02% > poultry litter 6.77% > poultry litter + compost 6.75% > poultry litter + bentonite 5.5% > poultry litter + biochar 3.4%. All emission factors exceeded the IPCC Tier 1 default for managed soils (1%) and the Australian Government default for sugarcane soil (1.25%). Our findings reinforce concerns that current default emissions factors underestimate N2O emissions. The laboratory incubations broadly matched the field N2O emissions, indicating that in vitro testing is a cost-effective first step to guide the blending of organic wastes in a way that ensures N sufficiency for crops but minimises N losses. We conclude that suitable sorbent-waste formulations that attenuate N release will advance N efficiency and the circular nutrient economy

Organic Wastes Amended with Sorbents Reduce N2O Emissions from Sugarcane Cropping

Nutrient-rich organic wastes and soil ameliorants can benefit crop performance and soil health but can also prevent crop nutrient sufficiency or increase greenhouse gas emissions. We hypothesised that nitrogen (N)-rich agricultural waste (poultry litter) amended with sorbents (bentonite clay or biochar) or compost (high C/N ratio) attenuates the concentration of inorganic nitrogen (N) in soil and reduces emissions of nitrous oxide (N2O). We tested this hypothesis with a field experiment conducted on a commercial sugarcane farm, using in vitro incubations. Treatments received 160 kg N ha−1, either from mineral fertiliser or poultry litter, with additional N (2–60 kg N ha−1) supplied by the sorbents and compost. Crop yield was similar in all N treatments, indicating N sufficiency, with the poultry litter + biochar treatment statistically matching the yield of the no-N control. Confirming our hypothesis, mineral N fertiliser resulted in the highest concentrations of soil inorganic N, followed by poultry litter and the amended poultry formulations. Reflecting the soil inorganic N concentrations, the average N2O emission factors ranked as per the following: mineral fertiliser 8.02% > poultry litter 6.77% > poultry litter + compost 6.75% > poultry litter + bentonite 5.5% > poultry litter + biochar 3.4%. All emission factors exceeded the IPCC Tier 1 default for managed soils (1%) and the Australian Government default for sugarcane soil (1.25%). Our findings reinforce concerns that current default emissions factors underestimate N2O emissions. The laboratory incubations broadly matched the field N2O emissions, indicating that in vitro testing is a cost-effective first step to guide the blending of organic wastes in a way that ensures N sufficiency for crops but minimises N losses. We conclude that suitable sorbent-waste formulations that attenuate N release will advance N efficiency and the circular nutrient economy

Bronchoalveolar lavage cytokines are of minor value to diagnose complications following lung transplantation

Early diagnosis and treatment of acute cellular rejection (ACR) may improve long-term outcome for lung transplant recipients (LTRs). Cytokines have become valuable diagnostic tools in many medical fields. The role of bronchoalveolar lavage (BAL) cytokines is of unknown value to diagnose ACR and distinguish rejection from infection. We hypothesized that distinct cytokine patterns obtained by surveillance bronchoscopies during the first year after transplantation are associated with ACR and microbiologic findings. We retrospectively analyzed data from 319 patients undergoing lung transplantation at University Hospital Zurich from 1998 to 2016. We compared levels of IL-6, IL-8, IFN-γ and TNF-α in 747 BAL samples with transbronchial biopsies (TBB) and microbiologic results from surveillance bronchoscopies. We aimed to define reference values that would allow distinction between four specific groups “ACR”, “infection”, “combined ACR and infection” and “no pathologic process”. No definitive pattern was identified. Given the overlap between groups, these four cytokines are not suitable diagnostic markers for ACR or infection after lung transplantation

Outcomes in patients with gunshot wounds to the brain.

Introduction:Gunshot wounds to the brain (GSWB) confer high lethality and uncertain recovery. It is unclear which patients benefit from aggressive resuscitation, and furthermore whether patients with GSWB undergoing cardiopulmonary resuscitation (CPR) have potential for survival or organ donation. Therefore, we sought to determine the rates of survival and organ donation, as well as identify factors associated with both outcomes in patients with GSWB undergoing CPR. Methods:We performed a retrospective, multicenter study at 25 US trauma centers including dates between June 1, 2011 and December 31, 2017. Patients were included if they suffered isolated GSWB and required CPR at a referring hospital, in the field, or in the trauma resuscitation room. Patients were excluded for significant torso or extremity injuries, or if pregnant. Binomial regression models were used to determine predictors of survival/organ donation. Results:825 patients met study criteria; the majority were male (87.6%) with a mean age of 36.5 years. Most (67%) underwent CPR in the field and 2.1% (n=17) survived to discharge. Of the non-survivors, 17.5% (n=141) were considered eligible donors, with a donation rate of 58.9% (n=83) in this group. Regression models found several predictors of survival. Hormone replacement was predictive of both survival and organ donation. Conclusion:We found that GSWB requiring CPR during trauma resuscitation was associated with a 2.1% survival rate and overall organ donation rate of 10.3%. Several factors appear to be favorably associated with survival, although predictions are uncertain due to the low number of survivors in this patient population. Hormone replacement was predictive of both survival and organ donation. These results are a starting point for determining appropriate treatment algorithms for this devastating clinical condition. Level of evidence:Level II

Overexpression of miRNA-25-3p inhibits Notch1 signaling and TGF-β-induced collagen expression in hepatic stellate cells

During chronic liver injury hepatic stellate cells (HSCs), the principal source of extracellular matrix in the fibrotic liver, transdifferentiate into pro-fibrotic myofibroblast-like cells - a process potentially regulated by microRNAs (miRNAs). Recently, we found serum miRNA-25-3p (miR-25) levels were upregulated in children with Cystic Fibrosis (CF) without liver disease, compared to children with CF-associated liver disease and healthy individuals. Here we examine the role of miR-25 in HSC biology. MiR-25 was detected in the human HSC cell line LX-2 and in primary murine HSCs, and increased with culture-induced activation. Transient overexpression of miR-25 inhibited TGF-β and its type 1 receptor (TGFBR1) mRNA expression, TGF-β-induced Smad2 phosphorylation and subsequent collagen1α1 induction in LX-2 cells. Pull-down experiments with biotinylated miR-25 revealed Notch signaling (co-)activators ADAM-17 and FKBP14 as miR-25 targets in HSCs. NanoString analysis confirmed miR-25 regulation of Notch- and Wnt-signaling pathways. Expression of Notch signaling pathway components and endogenous Notch1 signaling was downregulated in miR-25 overexpressing LX-2 cells, as were components of Wnt signaling such as Wnt5a. We propose that miR-25 acts as a negative feedback anti-fibrotic control during HSC activation by reducing the reactivity of HSCs to TGF-β-induced collagen expression and modulating the cross-talk between Notch, Wnt and TGF-β signaling

Bodyweight Perceptions among Texas Women: The Effects of Religion, Race/Ethnicity, and Citizenship Status

Despite previous work exploring linkages between religious participation and health, little research has looked at the role of religion in affecting bodyweight perceptions. Using the theoretical model developed by Levin et al. (Sociol Q 36(1):157–173, 1995) on the multidimensionality of religious participation, we develop several hypotheses and test them by using data from the 2004 Survey of Texas Adults. We estimate multinomial logistic regression models to determine the relative risk of women perceiving themselves as overweight. Results indicate that religious attendance lowers risk of women perceiving themselves as very overweight. Citizenship status was an important factor for Latinas, with noncitizens being less likely to see themselves as overweight. We also test interaction effects between religion and race. Religious attendance and prayer have a moderating effect among Latina non-citizens so that among these women, attendance and prayer intensify perceptions of feeling less overweight when compared to their white counterparts. Among African American women, the effect of increased church attendance leads to perceptions of being overweight. Prayer is also a correlate of overweight perceptions but only among African American women. We close with a discussion that highlights key implications from our findings, note study limitations, and several promising avenues for future research