The deteriorating in vivo environment is thought to play a major role in reduced stem cell function with age. The capacity of stem cells to support tissue maintenance depends not only on their response to cues from the surrounding niche, but also on their abundance. Here, we investigate satellite cell (myogenic stem cell) pool size and its potential to participate in muscle maintenance through old age. The numbers and performance of mouse satellite cells have been analyzed using molecular markers that exclusively characterize quiescent satellite cells and their progeny as they transit through proliferation, differentiation and generation of reserve cells. The study establishes that abundance of resident satellite cells declines with age in myofibers from both fast- and slow-twitch muscles. Nevertheless, the inherent myogenic potential of satellite cells does not diminish with age. Furthermore, the aging satellite cell niche retains the capacity to support effective myogenesis upon enrichment of the mitogenic milieu with FGF. Altogether, satellite cell abundance, but not myogenic potential, deteriorates with age. This study suggests that the population of satellite cells that participate in myofiber maintenance during routine muscle utilization is not fully replenished throughout life.
Mosquitoes, especially Aedes aegypti, are becoming important models for studying invasion biology. We characterized genetic variation at 12 microsatellite loci in 79 populations of Ae. aegypti, from 30 countries in six continents and used them to infer historical and modern patterns of invasion. Our results support the two subspecies Ae. aegypti formosus and Ae. aegypti aegypti as genetically distinct units. Ae. aegypti aegypti populations outside Africa are derived from ancestral African populations and are monophyletic. The two subspecies co-occur in both East Africa (Kenya) and West Africa (Senegal). In rural/forest settings (Rabai District of Kenya) the two subspecies remain genetically distinct whereas in urban settings they introgress freely. Populations outside Africa are highly genetically structured likely due to a combination of recent founder effects, discrete discontinuous habitats, and low migration rates. Ancestral populations in sub-Saharan Africa are less genetically structured, as are the populations in Asia. Introduction of Ae. aegypti to the New World coinciding with trans-Atlantic shipping in the 16th to 18th Centuries was followed by its introduction to Asia in the late 19th Century from the New World or from now extinct populations in the Mediterranean Basin. Aedes mascarensis is a genetically distinct sister species to Ae. aegypti s.l.. This study provides a reference database of genetic diversity that can be used to determine the likely origin of new introductions that occur regularly for this invasive species. The genetic uniqueness of many populations and regions has important implications for attempts to control Ae. aegypti, especially for methods using genetic modification of populations.
Repair of adult skeletal muscle depends on satellite cells, quiescent myogenic stem cells located beneath the myofiber basal lamina. Satellite cell numbers and performance decline with age and disease, yet the intrinsic molecular changes accompanying these conditions are unknown. We identified expression of GFP driven by regulatory elements of the nestin (NES) gene within mouse satellite cells, which permitted characterization of these cells in their niche. Sorted NES-GFP+ cells exclusively acquired a myogenic fate, even when supplemented with media supporting non-myogenic development. Mutual and unique gene expression by NES-GFP+ cells from hindlimb and diaphragm muscles demonstrated intra- and inter-muscular heterogeneity of satellite cells. NES-GFP expression declined following satellite cell activation and was reacquired in late stage myogenic cultures by non-proliferating Pax7+ progeny. The dynamics of this expression pattern reflect the cycle of satellite cell self-renewal. The NES-GFP model reveals unique transcriptional activity within quiescent satellite cells and permits novel insight into the heterogeneity of their molecular signatures.
Aedes albopictus, the “Asian tiger mosquito,” is an aggressive biting mosquito native to Asia that has colonized all continents except Antarctica during the last ~30–40 years. The species is of great public health concern as it can transmit at least 26 arboviruses, including dengue, chikungunya, and Zika viruses. In this study, using double‐digest Restriction site‐Associated DNA (ddRAD) sequencing, we developed a panel of ~58,000 single nucleotide polymorphisms (SNPs) based on 20 worldwide Ae. albopictus populations representing both the invasive and the native range. We used this genomic‐based approach to study the genetic structure and the differentiation of Ae. albopictus populations and to understand origin(s) and dynamics of the recent invasions. Our analyses indicated the existence of two major genetically differentiated population clusters, each one including both native and invasive populations. The detection of additional genetic structure within each major cluster supports that these SNPs can detect differentiation at a global and local scale, while the similar levels of genomic diversity between native and invasive range populations support the scenario of multiple invasions or colonization by a large number of propagules. Finally, our results revealed the possible source(s) of the recent invasion in Americas, Europe, and Africa, a finding with important implications for vector‐control strategies.
Biological systems produce phenotypes that appear to be robust to perturbation by mutations and environmental variation. Prior studies identified genes that, when impaired, reveal previously cryptic genetic variation. This result is typically interpreted as evidence that the disrupted gene normally increases robustness to mutations, as such robustness would allow cryptic variants to accumulate. However, revelation of cryptic genetic variation is not necessarily evidence that a mutationally robust state has been made less robust. Demonstrating a difference in robustness requires comparing the ability of each state (with the gene perturbed or intact) to suppress the effects of new mutations. Previous studies used strains in which the existing genetic variation had been filtered by selection. Here, we use mutation accumulation (MA) lines that have experienced minimal selection, to test the ability of histone H2A.Z (HTZ1) to increase robustness to mutations in the yeast Saccharomyces cerevisiae. HTZ1, a regulator of chromatin structure and gene expression, represents a class of genes implicated in mutational robustness. It had previously been shown to increase robustness of yeast cell morphology to fluctuations in the external or internal microenvironment. We measured morphological variation within and among 79 MA lines with and without HTZ1. Analysis of within-line variation confirms that HTZ1 increases microenvironmental robustness. Analysis of between-line variation shows the morphological effects of eliminating HTZ1 to be highly dependent on the line, which implies that HTZ1 interacts with mutations that have accumulated in the lines. However, lines without HTZ1 are, as a group, not more phenotypically diverse than lines with HTZ1 present. The presence of HTZ1, therefore, does not confer greater robustness to mutations than its absence. Our results provide experimental evidence that revelation of cryptic genetic variation cannot be assumed to be caused by loss of robustness, and therefore force reevaluation of prior claims based on that assumption.
Our understanding of the interaction between the gut microbiota and host health has recently improved dramatically. However, the effects of toxic metal exposure on the gut microbiota remain poorly characterized. As this microbiota creates a critical interface between the external environment and the host’s cells, it may play an important role in host outcomes during exposure. We therefore used 16S ribosomal RNA (rRNA) gene sequencing to track changes in the gut microbiota composition of rats exposed to heavy metals. Rats were exposed daily for five days to arsenic, cadmium, cobalt, chromium, nickel, or a vehicle control. Significant changes to microbiota composition were observed in response to high doses of chromium and cobalt, and significant dose-dependent changes were observed in response to arsenic, cadmium and nickel. Many of these perturbations were not uniform across metals. However, bacteria with higher numbers of iron-importing gene orthologs were overly represented after exposure to arsenic and nickel, suggesting some possibility of a shared response. These findings support the utility of the microbiota as a pre-clinical tool for identifying exposures to specific heavy metals. It is also clear that characterizing changes to the functional capabilities of microbiota is critical to understanding responses to metal exposure.
Abstract. The mosquito Aedes aegypti is a vector of yellow fever, dengue, and chikungunya. Control of the insect is crucial to stop the spread of dengue and chikungunya, so it is critically important to understand its mating behavior. Primarily, based on laboratory behavior, it has long been assumed that Ae. aegypti females mate once in their lifetime. However, multiple inseminations have been observed in semi-field and laboratory settings, and in closely related species. Here, we report the first evidence of polyandry in a natural population of Ae. aegypti. Female Ae. aegypti were captured around the New Orleans, LA, metropolitan area. They were offered a blood meal and allowed to lay eggs, which were reared to the third-instar larval stage. A parentage analysis using four microsatellite loci was performed. Out of 48 families, 3 showed evidence of multiple paternity. An expanded analysis of these three families found that one family group included offspring contributed by three fathers, and the other two included offspring from two fathers. This result establishes that polyandry can occur in a small proportion of Ae. aegypti females in a natural setting. This could complicate future genetic control efforts and has implications for sampling for population genetics.
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