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Biology subjects

Rose, N.

Publications and source records attributed to Rose, N..

8 recordsLinked to original sources

Rapid urban evolution of the dengue mosquito in West African cities

Aedes aegypti is an exceptionally effective global vector of human disease because of its strong specialization on human hosts and habitats. However, in its native range in Africa, many populations never specialized on humans and retained an ancestral generalist ecology. Now, in the rapidly growing cities of Kumasi, Ghana and Ouagadougou, Burkina Faso, we directly document genomic and behavioral evidence of a sudden shift towards greater specialization on humans over just five years. These changes are likely to enhance the ability of these urban mosquito populations to serve as effective vectors of human disease and may have played a role in unprecedented recent outbreaks of dengue fever in West African cities.

evolutionary biology↗

Drought tolerance of Aedes aegypti mosquito eggs is influenced by adaptation to local climate conditions and associations with humans

Urbanization is intensifying human interactions with mosquitoes, exacerbating public health challenges. Densely populated areas provide ideal conditions for container-dwelling mosquitoes, with increased host availability and the presence of artificial breeding sites. These anthropophilic mosquitoes often exhibit distinct ecological adaptations compared to their rural counterparts. Since mosquito eggs are immobile and remain at the site of oviposition, they provide a valuable lens for assessing how urbanization, climate-driven shifts in temperature, and drought affect mosquito reproductive success. This study examined Ae. aegypti egg viability under varying temperature and dry conditions over five months, focusing on lineages with distinct ancestries from West African populations. Mosquitoes collected from urban habitats with a high human preference demonstrated higher egg survival under prolonged arid conditions. Analysis of climatic factors revealed that dry season temperature and precipitation during wet periods are significant predictors of egg drought tolerance. Modeling future climate scenarios based on input from our egg viability results suggests a projected shift and expansion in the seasonal survival window for Ae. aegypti by the end of the century. This study highlights the importance of understanding environmental constraints on the drought tolerance of mosquito eggs to predict and mitigate future mosquito outbreaks.

physiology↗

An inducible tethered function assay reveals differential regulatory effects for the RNA-binding protein YBX3 and its domains.

RNA-binding protein (RBP) regulation is widespread across biology from development to learning and memory. Often RBPs contain multiple modular domains, which contribute to distinct RNA- binding activity or interactions necessary for regulation. However, assays to determine specific regulatory activity of individual domains are limited. The tethered function assay (TFA) provides a direct method to assess the functional activity of RBPs and their domains. The assay consists of two key components: (i) a reporter plasmid that encodes an mRNA, such as luciferase or GFP, engineered with high-affinity binding sites for an exogenous RNA-binding factor, and (ii) an effector construct that expresses a chimera of the RBP fused to the RNA-binding factor. Co- transfection of these constructs allows for measurement of reporter activity as a quantitative readout for RBP regulatory function. We developed an inducible TFA (iTFA) system through generation of a stable inducible mammalian cell line to express a reporter mRNA encoding nanoluciferase (nLuc) with six high-affinity MS2 binding sites within its 3 untranslated region. These cells can be transfected with a single plasmid that expresses an RBP fused to the MS2 coat protein. This approach enhances efficiency and reproducibility through reduction of transfection burden to a single plasmid and simplified normalization. We used this platform to dissect the individual and combined regulatory effects of YBX3 domains, a modular RBP with differential regulatory activity. The iTFA system provides a streamlined, tunable platform for functional analysis of RBPs that facilitates rapid interrogation of RBP or domain-specific activities in mammalian cells.

molecular biology↗

Genomic signatures of coral adaptation and recovery following a mass mortality event

Globally, corals face an increased frequency of mass mortality events (MMEs) as populations experience repeated marine heatwaves which disrupt their obligate algal symbiosis. Despite greater occurrences of MMEs, the relative roles of the environment, host, and symbiont genetic variation in survival and recovery remain unresolved. We explore these roles using high-resolution temporal and spatial whole genome sequencing of corals before, after, and several years following a MME. We show that host genetics has an impact on bleaching and mortality and that selected alleles important for adaptation persist through the next generation. We also demonstrate that survival for the bleaching event was highly polygenic and that allele frequency shifts have reef habitat specificity. This study reveals how MMEs reshape the genomic landscape and the spatial and temporal distribution of genomic diversity within coral populations facing severe threats from global change. SIGNIFICANCEInvestigations of natural selection in coral genomes following bleaching events have primarily relied on indirect inference, using contemporary populations to explore signatures of past selective pressures, or failed to link these events to the subsequent generation. This has left an open question about the ability of a coral population to adapt from host standing genetic variation in the face of a bleaching event. We demonstrate rapid evolution in a Moorean coral population following an MME from a marine heatwave by capturing allele frequency shifts through time. However, the complex polygenic architecture of bleaching survival shows strong habitat specificity, complicating the path towards a genomic prediction of bleaching.

evolutionary biology↗

A multi-host mechanistic model of African swine fever emergence and control in Romania

African swine fever (ASF) has devastating effects on swine production, farmer livelihood, animal welfare, and biodiversity. Extremely difficult to control, epidemic management is further complicated when spillover between domestic pig and wild boar populations is suspected. To quantify ASF viral transmission between domestic pigs and wild boar, a spatially-explicit stochastic mechanistic model was constructed using village centroids to represent aggregated backyard pig herds and a hexagonal raster of forest coverage to represent wild boar abundance. The model was parameterized to the initial six months of the ongoing Romanian epidemic through approximate Bayesian computation. It was estimated that a median of 69.4% (interquartile range: 53.0-80.0%) of domestic pig herd cases came from other infected domestic pig herds while 20.4% (11.2-33.8%) originated from infected wild boar sources, and 8.4% (4.7-14.2%) stemmed from external sources not explicitly represented. Also, 31.9% of infected wild boar habitat (16.7-56.2%) originated from domestic pig herds and 68.1% (43.8-83.3%) came from neighboring infected wild boar populations. Furthermore, it was found that habitats with a forest coverage greater than 15% were 2.6 times more infectious and 5.3 times more susceptible than other habitats. All alternative control scenarios, including culling domestic pig herds upon local domestic pig or wild boar case detection, improved epidemic outcomes, with the greatest decrease in final epidemic size being observed from the reactive culling of entire villages following case detection. These results can be used to further inform policy recommendations in ASF-epidemic regions. Significance StatementThe current African swine fever (ASF) pandemic is devastating to affected nations, and quantifying transmission parameters is critical to informing control strategies. Disease spillover between wild and domestic hosts further complicates control efforts, yet the influence of spillover events on epidemic propagation remains unknown. Using the context of Romania--one of the European nations with the most severe epidemic and where spillover transmission is strongly suspected--we show that targeting spillover mechanisms is critical for achieving holistic disease control, and then demonstrate the impact of alternative control scenarios had they been enacted. These results can inform control strategy policy decisions in the many nations at-risk for or actively experiencing ASF epidemics.

ecology↗

Extensive variation and strain-specificity in dengue virus susceptibility among African Aedes aegypti populations

African populations of the mosquito Aedes aegypti are usually considered less susceptible to infection by human-pathogenic flaviviruses than globally invasive populations found outside Africa. Although this contrast has been well documented for Zika virus (ZIKV), it is unclear to what extent it is true for dengue virus (DENV), the most prevalent flavivirus of humans. Addressing this question is complicated by substantial genetic diversity among DENV strains, most notably in the form of four genetic types (DENV1 to DENV4), that can lead to genetically specific interactions with mosquito populations. Here, we carried out a continent-wide survey of DENV susceptibility using a panel of field-derived Ae. aegypti colonies from across the African range of the species and a colony from Guadeloupe, French West Indies as non-African reference. We found considerable variation in the ability of African Ae. aegypti populations to acquire and replicate a panel of six DENV strains spanning the four DENV types. Although African Ae. aegypti populations were generally less susceptible than the reference non-African population from Guadeloupe, in several instances some African populations were equally or more susceptible than the Guadeloupe population. Moreover, the relative level of susceptibility between African mosquito populations depended on the DENV strain, indicating genetically specific interactions. We conclude that unlike ZIKV susceptibility, there is no clear-cut dichotomy in DENV susceptibility between African and non-African Ae. aegypti. DENV susceptibility of African Ae. aegypti populations is highly heterogeneous and largely governed by the specific pairing of mosquito population and DENV strain. Author summaryAfrican populations of the mosquito Aedes aegypti are usually thought to be less likely to get infected by flaviviruses compared to Ae. aegypti mosquitoes found outside Africa. While this has been well-demonstrated for Zika virus, it is not clear if the same is true for dengue virus, which is the most common flavivirus in humans. Studying this is complicated by the strain diversity of dengue virus, including four main genetic types, potentially causing different interactions. In this study, we compared several mosquito populations and found that, in general, African mosquitoes were less likely to get infected by dengue virus compared to mosquitoes from outside Africa. However, in some cases, African mosquitoes were just as or even more likely to get infected. The specific strain of dengue virus also influenced how likely African mosquitoes were to get infected, showing that the relationship between African mosquitoes and dengue virus is complex.

microbiology↗

Bioengineering a Miniaturized In Vitro 3D Myotube Contraction Monitoring Chip For Modelization of Muscular Dystrophies

Quantification of skeletal muscle functional contraction is essential to assess the outcomes of therapeutic procedures for muscular disorders. Muscle three-dimensional "Organ-on-chip" models usually require a substantial amount of biological material, which is problematic in the context of limited patient sample. Here we developed a miniaturized 3D myotube culture chip with contraction monitoring capacity. Optimized micropatterned substrate design enabled to obtain high culture yields in tightly controlled microenvironments. Spontaneous contractions in myotubes derived from primary human myoblasts were observed. Analysis of nuclear morphology confirmed a similar organization between obtained myotubes and in vivo myofibers. LMNA-related Congenital Muscular Dystrophy (L-CMD) was modelled with successful development of mutant 3D myotubes displaying contractile dysfunction. This technology can thus be used to study contraction characteristics and evaluate how diseases affect muscle organization and force generation. Importantly, it requires significantly fewer starting materials than current systems, which should allow to substantially improve drug screening capability.

bioengineering↗

Differential myoblast and tenoblast affinity to collagen, fibrin and mixed threads in the prospect of muscle-tendon junction modelisation

The myotendinous junction transfers forces from muscle to tendon. As such, it must hold two tissues of completely different biological and cellular compositions as well as mechanical properties (kPa-MPa to MPa-GPa) and is subject to frequent stresses of high amplitude. This region remains a weak point of the muscle-tendon unit and is involved in frequent injuries. We here produce fibrin (40 mg/mL, E0 =0.10 {+/-} 0.02 MPa) and collagen (60 mg/mL, E0=0.57 {+/-} 0.05 MPa) threads as well as mixed collagen:fibrin threads (3:2 in mass, E0 = 0.33 {+/-} 0.05 MPa) and investigate the difference of affinity between primary murine myoblasts and tenoblasts. We demonstrate a similar behavior of cells on mixed and fibrin threads with high adherence of tenoblasts and myoblasts, in comparison to collagen threads that promote high adherence and proliferation of tenoblasts but not of myoblasts. Besides, we show that myoblasts on threads differentiate but do not fuse, on the contrary to 2D control substrates, raising the question of the effect of substrate curvature on the ability of myoblasts to fuse in vitro.

bioengineering↗