Generalizations of the Moran effect explaining spatial synchrony in population fluctuations

The Moran effect for populations separated in space states that the autocorrelations in the population fluctuations equal the autocorrelation in environmental noise, assuming the same linear density regulation in all populations. Here we generalize the Moran effect to include also nonlinear density regulation with spatial heterogeneity in local population dynamics as well as in the effects of environmental covariates by deriving a simple expression for the correlation between the sizes of two populations, using diffusion approximation to the theta-logistic model. In general, spatial variation in parameters describing the dynamics reduces population synchrony. We also show that the contribution of a covariate to spatial synchrony depends strongly on spatial heterogeneity in the covariate or in its effect on local dynamics. These analyses show exactly how spatial environmental covariation can synchronize fluctuations of spatially segregated populations with no interchange of individuals even if the dynamics are nonlinear.     

A dynamic and spatial model with migration generating the log-Gaussian field of population densities

A spatial version of a dynamic population model leading to the lognormal distribution is defined. The model establishes relations between the joint spatial and temporal autocorrelation and biological concepts like environmental stochasticity, migration and strength of local density-regulation. The model is generalized to describe communities of species leading to a dynamic and spatial lognormal species abundance model with migration.     

Intramolecular binding of a proximal PPII helix to an SH3 domain in the fusion protein SH3Hck: PPIIhGAP

SH3 domains are a conserved feature of many nonreceptor protein tyrosine kinases, such as Hck, and often function in substrate recruitment and regulation of kinase activity. SH3 domains modulate kinase activity by binding to polyproline helices (PP_II helix) either intramolecularly or in target proteins. The preponderance of bimolecular and distal interactions between SH3 domains and PP_II helices led us to investigate whether proximal placement of a PP_II helix relative to an SH3 domain would result in tight, intramolecular binding. We have fused the PP_II helix region of human GAP to the C-terminus of Hck SH3 and expressed the recombinant fusion protein in Eschericheria coli. The fusion protein, SH3_Hck: PPII_hGAP, folded spontaneously into a structure in which the PP_II helix was bound intramolecularly to the hydrophobic crevice of the SH3 domain. The SH3_Hck: PPII_hGAP fusion protein is useful for investigating SH3: PP_II helix interactions, for studying concepts in protein folding and design, and may represent a protein structural motif that is widely distributed in nature.     

Double Embedding Again

A method of double embedding fixed tissues in 3% low viscosity nitrocellulose and paraffin is described. Five percent phenol in 80% alcohol during dehydration and 5% glycerin in the nitrocellulose solutions enhance cutting qualities. A modified Ruyter's solution is used to flatten sections. After a section is aflixed to a slide, it is passed through chloroform and acetone to remove the paraftin and celloidin. A 1% celloidin dip insures adherence of the seaion to the slide. Slides are stored in 70% alcohol until they are to be stained. Following staining and dehydration in graded alcohols, clearing should be done in a 1: 3 mixture of terpineol and toluene.     

Temperature during early development has long-term effects on microRNA expression in Atlantic cod

Background

Environmental temperature has serious implications in life cycle of aquatic ectotherms. Understanding the molecular mechanisms of temperature acclimation and adaptation of marine organisms is of the uttermost importance for ecology, fisheries, and aquaculture, as it allows modeling the effects of global warming on population dynamics. Regulatory molecules are major modulators of acclimation and adaptation; among them, microRNAs (miRNAs) are versatile and substantial contributors to regulatory networks of development and adaptive plasticity. However, their role in thermal plasticity is poorly known. We have asked whether the temperature and its shift during the early ontogeny (embryonic and larval development) affect the miRNA repertoire of Atlantic cod (Gadus morhua), and if thermal experience has long-term consequences in the miRNA profile.

Results

We characterized miRNA during different developmental stages and in juvenile tissues using next generation sequencing. We identified 389 putative miRNA precursor loci, 120 novel precursor miRNAs, and 281 mature miRNAs. Some miRNAs showed stage- or tissue-enriched expression and miRNAs, such as the miR-17 ~ 92 cluster, myomiRs (miR-206), neuromiRs (miR-9, miR-124), miR-130b, and miR-430 showed differential expression in different temperature regimes. Long-term effect of embryonic incubation temperature was revealed on expression of some miRNAs in juvenile pituitary (miR-449), gonad (miR-27c, miR-30c, and miR-200a), and liver (let-7 h, miR-7a, miR-22, miR-34c, miR-132a, miR-192, miR-221, miR-451, miR-2188, and miR-7550), but not in brain. Some of differentially expressed miRNAs in the liver were confirmed using LNA-based rt-qPCR. The effect of temperature on methylation status of selected miRNA promoter regions was mostly inconclusive.

Conclusions

Temperature elevation by several degrees during embryonic and larval developmental stages significantly alters the miRNA profile, both short-term and long-term. Our results suggest that a further rise in seas temperature might affect life history of Atlantic cod.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1503-7) contains supplementary material, which is available to authorized users.     

Interspecific differences in stochastic population dynamics explains variation in Taylor's temporal power law

Taylor’s power law, i.e. that the slope for the increase in variance with mean population size is between 1 and 2 at a logarithmic scale, provides one of the few quantitative relationships in population ecology, yet the underlying ecological mechanisms are only poorly understood. Stochastic theory of population dynamics predicts that demographic and environmental stochasticity will affect the slope differently. In a stable environment under the influence of demographic stochasticity alone the slope will be equal to 1. In large populations in which demographic variance will have a negligible effect on the dynamics the slope will approach 2. In addition, the slope will also be influenced by how the strength of density dependence is related to mean population size. To disentangle the relative contribution of these processes we estimate the mean‐variance relationship for a large number of populations of British birds. The variance in population size of most species decreased with the mean due to decreased influence of demographic stochasticity at larger population sizes. Interspecific differences in demographic stochasticity was the main factor influencing variation in slopes of Taylor’s power law among species through a significant negative relationship between the slope and demographic variance. In addition, slopes were influenced by interspecific variation in life history parameters such as adult survival and clutch size. These analyses show that Taylor’s power law is generated from an interplay between stochastic and density dependent factors, modulated by life history.     

Evolution of a plastic quantitative trait in an age-structured population in a fluctuating environment

We analyze weak fluctuating selection on a quantitative character in an age-structured population not subject to density regulation. We assume that early in the first year of life before selection, during a critical state of development, environments exert a plastic effect on the phenotype, which remains constant throughout the life of an individual. Age-specific selection on the character affects survival and fecundity, which have intermediate optima subject to temporal environmental fluctuations with directional selection in some age classes as special cases. Weighting individuals by their reproductive value, as suggested by Fisher, we show that the expected response per year in the weighted mean character has the same form as for models with no age structure. Environmental stochasticity generates stochastic fluctuations in the weighted mean character following a first-order autoregressive model with a temporally autocorrelated noise term and stationary variance depending on the amount of phenotypic plasticity. The parameters of the process are simple weighted averages of parameters used to describe age-specific survival and fecundity. The "age-specific selective weights" are related to the stable distribution of reproductive values among age classes. This allows partitioning of the change in the weighted mean character into age-specific components.     

Identification and Characterization of Cells with Cancer Stem Cell Properties in Human Primary Lung Cancer Cell Lines

Lung cancer (LC) with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs) within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs) from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC), large cell carcinoma (LCC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). We identified a small population of cells strongly positive for CD44 (CD44^high) and a main population which was either weakly positive or negative for CD44 (CD44^low/−). Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44^highCD90⁺ sub-population. Moreover, these CD44^highCD90⁺ cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44^highCD90⁺ population a good candidate for the lung CSCs. Both CD44^highCD90⁺ and CD44^highCD90⁻ cells in the PLCCL derived from SCC formed spheroids, whereas the CD44^low/− cells were lacking this potential. These results indicate that CD44^highCD90⁺ sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44^high sub-population.     

Capacity and Adaptations of General Practice during an Influenza Pandemic

Background

GPs play a major role in influenza epidemics, and most patients with influenza-like-illness (ILI) are treated in general practice or by primary care doctors on duty in out-of-hours services (OOH). Little is known about the surge capacity in primary care services during an influenza pandemic, and how the relationship between them changes.

Aim

To investigate how general practice and OOH services were used by patients during the 2009 pandemic in Norway and the impact of the pandemic on primary care services in comparison to a normal influenza season.

Materials

Data from electronic remuneration claims from all OOH doctors and regular GPs for 2009.

Methods

We conducted a registry-based study of all ILI consultations in the 2009 pandemic with the 2008/09 influenza season (normal season) as baseline for comparison.

Results

The majority (82.2%) of ILI consultations during the 2009 pandemic took place in general practice. The corresponding number in the 2008/09 season was 89.3%. Compared with general practice, the adjusted odds ratio for ILI with all other diagnoses as reference in OOH services was 1.23 (95% CI, 1.18, 1.27) for the 2008/2009 season and 1.87 (95% CI, 1.84, 1.91) for the pandemic influenza season. In total there was a 3.3-fold increase in ILI consultations during the pandemic compared to the 2008/09 season. A 5.5-fold increase of ILI consultations were observed in OOH services in comparison to the 2008/09 season. Children and young adults with ILI were the most frequent users of OOH services during influenza periods.

Conclusions

The autumn pandemic wave resulted in a significantly increased demand on primary care services. However, GPs in primary care services in Norway showed the ability to increase capacity in a situation with increased patient demand.     

Cumulative deamidations of the major lens protein γS‐crystallin increase its aggregation during unfolding and oxidation

Age‐related lens cataract is the major cause of blindness worldwide. The mechanisms whereby crystallins, the predominant lens proteins, assemble into large aggregates that scatter light within the lens, and cause cataract, are poorly understood. Due to the lack of protein turnover in the lens, crystallins are long‐lived. A major crystallin, γS, is heavily modified by deamidation, in particular at surface‐exposed N14, N76, and N143 to introduce negative charges. In this present study, deamidated γS was mimicked by mutation with aspartate at these sites and the effect on biophysical properties of γS was assessed via dynamic light scattering, chemical and thermal denaturation, hydrogen‐deuterium exchange, and susceptibility to disulfide cross‐linking. Compared with wild type γS, a small population of each deamidated mutant aggregated rapidly into large, light‐scattering species that contributed significantly to the total scattering. Under partially denaturing conditions in guanidine hydrochloride or elevated temperature, deamidation led to more rapid unfolding and aggregation and increased susceptibility to oxidation. The triple mutant was further destabilized, suggesting that the effects of deamidation were cumulative. Molecular dynamics simulations predicted that deamidation augments the conformational dynamics of γS. We suggest that these perturbations disrupt the native disulfide arrangement of γS and promote the formation of disulfide‐linked aggregates. The lens‐specific chaperone αA‐crystallin was poor at preventing the aggregation of the triple mutant. It is concluded that surface deamidations cause minimal structural disruption individually, but cumulatively they progressively destabilize γS‐crystallin leading to unfolding and aggregation, as occurs in aged and cataractous lenses.