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1. How differing modes of non‐genetic inheritance affect population viability in fluctuating environments

   https://doi.org/10.1111/ele.13355  

   Proulx, Stephen R.; Dey, Snigdhadip; Guzella, Thiago; Teotónio, Henrique; Coulson, ed., Tim (August 2019, Ecology Letters)

   Abstract Different modes of non‐genetic inheritance are expected to affect population persistence in fluctuating environments. We here analyseCaenorhabditis elegansdensity‐independent per capita growth rate time series on 36 populations experiencing six controlled sequences of challenging oxygen level fluctuations across 60 generations, and parameterise competing models of non‐genetic inheritance in order to explain observed dynamics. Our analysis shows that phenotypic plasticity and anticipatory maternal effects are sufficient to explain growth rate dynamics, but that a carryover model where ‘epigenetic’ memory is imperfectly transmitted and might be reset at each generation is a better fit to the data. We further find that this epigenetic memory is asymmetric since it is kept for longer when populations are exposed to the more challenging environment. Our analysis suggests that population persistence in fluctuating environments depends on the non‐genetic inheritance of phenotypes whose expression is regulated across multiple generations. 

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2. HIV efficiently infects T cells from the endometrium and remodels them to promote systemic viral spread

   https://doi.org/10.7554/eLife.55487  

   Ma, Tongcui; Luo, Xiaoyu; George, Ashley F; Mukherjee, Gourab; Sen, Nandini; Spitzer, Trimble L; Giudice, Linda C; Greene, Warner C; Roan, Nadia R (May 2020, eLife)

   The female reproductive tract (FRT) is the most common site of infection during HIV transmission to women, but viral remodeling complicates characterization of cells targeted for infection. Here, we report extensive phenotypic analyses of HIV-infected endometrial cells by CyTOF, and use a ‘nearest neighbor’ bioinformatics approach to trace cells to their original pre-infection phenotypes. Like in blood, HIV preferentially targets memory CD4+ T cells in the endometrium, but these cells exhibit unique phenotypes and sustain much higher levels of infection. Genital cell remodeling by HIV includes downregulating TCR complex components and modulating chemokine receptor expression to promote dissemination of infected cells to lymphoid follicles. HIV also upregulates the anti-apoptotic protein BIRC5, which when blocked promotes death of infected endometrial cells. These results suggest that HIV remodels genital T cells to prolong viability and promote viral dissemination and that interfering with these processes might reduce the likelihood of systemic viral spread. 

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3. Measuring regulatory network inheritance in dividing yeast cells using ordinary differential equations

   https://doi.org/10.1101/2024.11.23.624995  

   Wu, Wenbin; Kennedy, Taylor; Arguello-Miranda, Orlando; Lin, Kevin Z (November 2024, bioRxiv)

   Abstract Quantifying the inheritance of regulatory networks among proteins during asymmetric cell division remains a challenge due to the complexity of these systems and the lack of robust mathematical definitions for inheritance. We propose a novel statistical framework called ODEinherit to measure how much a mother cell’s regulatory network explains its daughter’s trajectories, addressing this gap. Using time-lapse microscopy, we tracked the expression dynamics of six proteins across 85 dividingS. cerevisiaecells, observed over eight hours at 12-minute intervals. Our framework employs a two-step approach. First, we estimate an ordinary differential equation (ODE) system for each cell to characterize protein interactions, introducing novel adjustments for non-oscillatory time series and leveraging multi-cell data. Second, we assess inheritance by clustering cells based on cycling markers and quantifying how well a mother’s regulatory network predicts her daughter’s. Preliminary findings suggest stage-dependent differences in inheritance rates, paving the way for applications in cellular stress response and cell-fate prediction studies across generations. 

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4. A deficiency screen of the 3rd chromosome for dominant modifiers of the Drosophila ER integral membrane protein, Jagunal

   https://doi.org/10.1093/g3journal/jkad059  

   Ascencio, Gerson; de Cruz, Matthew A.; Abuel, Judy; Alvarado, Sydney; Arriaga, Yuma; Conrad, Emily; Castro, Alonso; Eichelberger, Katharine; Galvan, Laura; Gundy, Grace; et al (March 2023, G3: Genes, Genomes, Genetics)

   Abstract The mechanism surrounding chromosome inheritance during cell division has been well documented, however, organelle inheritance during mitosis is less understood. Recently, the endoplasmic reticulum (ER) has been shown to reorganize during mitosis, dividing asymmetrically in proneuronal cells prior to cell fate selection, indicating a programmed mechanism of inheritance. ER asymmetric partitioning in proneural cells relies on the highly conserved ER integral membrane protein, Jagunal (Jagn). Knockdown of Jagn in the compound Drosophila eye displays a pleotropic rough eye phenotype in 48% of the progeny. To identify genes involved in Jagn dependent ER partitioning pathway, we performed a dominant modifier screen of the 3rd chromosome for enhancers and suppressors of this Jagn-RNAi-induced rough eye phenotype. We screened through 181 deficiency lines covering the 3L and 3R chromosomes and identified 12 suppressors and 10 enhancers of the Jagn-RNAi phenotype. Based on the functions of the genes covered by the deficiencies, we identified genes that displayed a suppression or enhancement of the Jagn-RNAi phenotype. These include Division Abnormally Delayed (Dally), a heparan sulfate proteoglycan, the γ-secretase subunit Presenilin, and the ER resident protein Sec63. Based on our understanding of the function of these targets, there is a connection between Jagn and the Notch signaling pathway. Further studies will elucidate the role of Jagn and identified interactors within the mechanisms of ER partitioning during mitosis. 

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5. Galbut Virus Infection Minimally Influences Drosophila melanogaster Fitness Traits in a Strain and Sex-Dependent Manner

   https://doi.org/10.3390/v15020539  

   Cross, Shaun T.; Brehm, Ali L.; Dunham, Tillie J.; Rodgers, Case P.; Keene, Alexandra H.; Borlee, Grace I.; Stenglein, Mark D. (February 2023, Viruses)

   Galbut virus (family Partitiviridae) infects Drosophila melanogaster and can be transmitted vertically from infected mothers or infected fathers with near perfect efficiency. This form of super-Mendelian inheritance should drive infection to 100% prevalence, and indeed, galbut virus is ubiquitous in wild D. melanogaster populations. However, on average, only about 60% of individual flies are infected. One possible explanation for this is that a subset of flies are resistant to infection. Although galbut virus-infected flies appear healthy, infection may be sufficiently costly to drive selection for resistant hosts, thereby decreasing overall prevalence. To test this hypothesis, we quantified a variety of fitness-related traits in galbut virus-infected flies from two lines from the Drosophila Genetic Reference Panel (DGRP). Galbut virus-infected flies had no difference in average lifespan and total offspring production compared to their uninfected counterparts. Galbut virus-infected DGRP-517 flies pupated and eclosed faster than their uninfected counterparts. Some galbut virus-infected flies exhibited altered sensitivity to viral, bacterial, and fungal pathogens. The microbiome composition of flies was not measurably perturbed by galbut virus infection. Differences in phenotype attributable to galbut virus infection varied as a function of fly sex and DGRP strain, and differences attributable to infection status were dwarfed by larger differences attributable to strain and sex. Thus, galbut virus infection does produce measurable phenotypic changes, with changes being minor, offsetting, and possibly net-negative. 

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