scholarly journals The impact of artificial selection for Wolbachia-mediated dengue virus blocking on phage WO

2021 ◽  
Vol 15 (7) ◽  
pp. e0009637
Author(s):  
Heverton L. C. Dutra ◽  
Suzanne A. Ford ◽  
Scott L. Allen ◽  
Sarah R. Bordenstein ◽  
Stephen F. Chenoweth ◽  
...  

Wolbachia is currently at the forefront of global efforts to control arbovirus transmission from the vector Aedes aegypti. The use of Wolbachia relies on two phenotypes—cytoplasmic incompatibility (CI), conferred by cifA and cifB genes in prophage WO, and Wolbachia-mediated pathogen blocking (WMPB). These traits allow for local, self-sustaining reductions in transmission of dengue (DENV) following release of Wolbachia-infected A. aegypti. Here, aided by previous artificial selection experiment that generated Low and High pathogen blocking lines, we examined the potential link between WMPB and phage WO. We found no evidence that Wolbachia or phage WO relative densities predict DENV blocking strength across selected lines. However, selection resulted in reduced phage WO relative density for the Low WMPB line. The Low blocking line was previously shown to have reduced fitness as a result of selection. Through subsequent genomic analyses, we demonstrate that SNP variation underpinning selection for low blocking led to elevated frequency of potential deleterious SNPs on chromosome 1. The key region on chromosome 1 contains genes relating to cell cycle regulation, oxidative stress, transcriptional pausing, among others, that may have cascading effects on Wolbachia intracellular environment. We hypothesize that reduction in phage WO may be driven by changes in the loci directly under selection for blocking, or by the accumulation of predicted deleterious alleles in linkage disequilibrium with blocking loci resulting from hitchhiking. For the Low line with fewer phage WO, we also detected reduced expression of cifA and cifB CI genes, with patterns of expression varying between somatic and reproductive tissues. In conclusion, we propose that artificial selection for WMPB trait had corresponding impacts on phage WO densities, and also the transcription of CI-causing genes. Future studies may include a more detailed analysis of the regions the A. aegypti chromosome 1’s ability to affect WMPB and other Wolbachia-associated intrinsic factors such as phage WO.

2021 ◽  
Vol 12 ◽  
Author(s):  
Martijn F. L. Derks ◽  
Marije Steensma

Harmful alleles can be under balancing selection due to an interplay of artificial selection for the variant in heterozygotes and purifying selection against the variant in homozygotes. These pleiotropic variants can remain at moderate to high frequency expressing an advantage for favorable traits in heterozygotes, while harmful in homozygotes. The impact on the population and selection strength depends on the consequence of the variant both in heterozygotes and homozygotes. The deleterious phenotype expressed in homozygotes can range from early lethality to a slightly lower fitness in the population. In this review, we explore a range of causative variants under balancing selection including loss-of-function variation (i.e., frameshift, stop-gained variants) and regulatory variation (affecting gene expression). We report that harmful alleles often affect orthologous genes in different species, often influencing analogous traits. The recent discoveries are mainly driven by the increasing genomic and phenotypic resources in livestock populations. However, the low frequency and sometimes subtle effects in homozygotes prevent accurate mapping of such pleiotropic variants, which requires novel strategies to discover. After discovery, the selection strategy for deleterious variants under balancing selection is under debate, as variants can contribute to the heterosis effect in crossbred animals in various livestock species, compensating for the loss in purebred animals. Nevertheless, gene-assisted selection is a useful tool to decrease the frequency of the harmful allele in the population, if desired. Together, this review marks various deleterious variants under balancing selection and describing the functional consequences at the molecular, phenotypic, and population level, providing a resource for further study.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 210
Author(s):  
Lise Vandevivere ◽  
Maxine Vangampelaere ◽  
Christoph Portier ◽  
Cedrine de Backere ◽  
Olaf Häusler ◽  
...  

The suitability of pharmaceutical binders for continuous twin-screw wet granulation was investigated as the pharmaceutical industry is undergoing a switch from batch to continuous manufacturing. Binder selection for twin-screw wet granulation should rely on a scientific approach to enable efficient formulation development. Therefore, the current study identified binder attributes affecting the binder effectiveness in a wet granulation process of a highly soluble model excipient (mannitol). For this formulation, higher binder effectiveness was linked to fast activation of the binder properties (i.e., fast binder dissolution kinetics combined with low viscosity attributes and good wetting properties by the binder). As the impact of binder attributes on the granulation process of a poorly soluble formulation (dicalcium phosphate) was previously investigated, this enabled a comprehensive comparison between both formulations in current research focusing on binder selection. This comparison revealed that binder attributes that are important to guide binder selection differ in function of the solubility of the formulation. The identification of critical binder attributes in the current study enables rational and efficient binder selection for twin-screw granulation of well soluble and poorly soluble formulations. Binder addition proved especially valuable for a poorly soluble formulation.


2021 ◽  
pp. 1-15
Author(s):  
Luis Sánchez

Abstract In Descent of Man, Charles Darwin noted the impact of political institutions on natural selection. He thought that institutions such as asylums or hospitals may deter natural selection; however, he did not reach a decisive answer. Questions remain as to whether the selective impacts of political institutions, which in Darwin’s terms may be referred to as “artificial selection,” are compatible with natural selection, and if so, to what extent. This essay argues that currently there appears to be an essential mismatch between nature and political institutions. Unfitted institutions put exogenous and disproportionate pressures on living beings. This creates consequences for what is postulated as the condition of basic equivalence, which allows species and individuals to enjoy similar chances of survival under natural circumstances. Thus, contrary to Darwin’s expectations, it is sustained that assumed natural selection is not discouraged but becomes exacerbated by political institutions. In such conditions, selection becomes primarily artificial and perhaps mainly political, with consequences for species’ evolutionary future.


2021 ◽  
Vol 12 (2) ◽  
pp. 491-502
Author(s):  
Sarah R. Bloor ◽  
Rudolph Schutte ◽  
Anthony R. Hobson

Iron deficiency anaemia (IDA) is a worldwide healthcare problem affecting approximately 25% of the global population. The most common IDA treatment is oral iron supplementation, which has been associated with gastrointestinal (GI) side effects such as constipation and bloating. These can result in treatment non-adherence and the persistence of IDA. Intravenous iron does not cause GI side effects, which may be due to the lack of exposure to the intestinal lumen. Luminal iron can cause changes to the gut microbiota, aiding the promotion of pathogenic species and decreasing beneficial protective species. Iron is vital for methanogenic archaea, which rely on iron for growth and metabolism. Increased intestinal methane has been associated with slowing of intestinal transit, constipation, and bloating. Here we explore the literature to understand a potential link between iron and methanogenesis as a novel way to understand the mechanism of oral iron supplementation induced GI side effects.


Genetics ◽  
2013 ◽  
Vol 196 (3) ◽  
pp. 829-840 ◽  
Author(s):  
Timothy M. Beissinger ◽  
Candice N. Hirsch ◽  
Brieanne Vaillancourt ◽  
Shweta Deshpande ◽  
Kerrie Barry ◽  
...  

2016 ◽  
Vol 64 (8) ◽  
pp. 643 ◽  
Author(s):  
Christopher N. Johnson

Since the 1960s, Australian scientists have speculated on the impact of human arrival on fire regimes in Australia, and on the relationship of landscape fire to extinction of the Pleistocene megafauna of Australia. These speculations have produced a series of contrasting hypotheses that can now be tested using evidence collected over the past two decades. In the present paper, I summarise those hypotheses and review that evidence. The main conclusions of this are that (1) the effects of people on fire regimes in the Pleistocene were modest at the continental scale, and difficult to distinguish from climatic controls on fire, (2) the arrival of people triggered extinction of Australia’s megafauna, but fire had little or no role in the extinction of those animals, which was probably due primarily to hunting and (3) megafaunal extinction is likely to have caused a cascade of changes that included increased fire, but only in some environments. We do not yet understand what environmental factors controlled the strength and nature of cascading effects of megafaunal extinction. This is an important topic for future research.


2006 ◽  
Vol 35 ◽  
pp. 247-250
Author(s):  
H. Randle ◽  
E. Elworthy

The influence of Natural Selection on the evolution of the horse (Equus callabus) is minimal due to its close association with humans. Instead Artificial Selection is commonly imposed through selection for features such as a ‘breed standard’ or competitive ability. It has long been considered to be useful if indicators of characteristics such as physical ability could be identified. Kidd (1902) suggested that the hair coverings of animals were closely related to their lifestyle, whether they were active or passive. In 1973 Smith and Gong concluded that hair whorl (trichloglyph) pattern and human behaviour is linked since hair patterning is determined at the same time as the brain develops in the foetus. More recently Grandin et al. (1995), Randle (1998) and Lanier et al. (2001) linked features of facial hair whorls to behaviour and production in cattle. Hair whorl features have also been related to temperament in equines (Randle et al., 2003).


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