bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cold stress upregulates the expression of heat shock and Frost genes, but the evolution of cold stress resistance is apparently not mediated through either heat shock or Frost genes in the cold stress selected populations of Drosophila melanogaster
Authors: Singh Karan , Prasad Nagaraj Guru 
Published: March 2022

AbstractThe ability to thermal adaptation can alter insects’ reproductive traits and physiologic response. A number of studies in Drosophila documented the higher expression levels of heat shock proteins (Hsps) and Frost (Fst) genes during the recovery phase of cold shock treatment and suggested that higher expression levels of these genes and lipids can protect from cold stress. However, these genes’ expression and cold adaptation have not been well studied. Therefore, understanding the molecular and biochemical basis of cold adaptation, we examined the levels of lipid and expression patterns of Hsp22, Hsp23, Hsp40, Hsp68, Hsp70, Hsp 83, and Fst genes under the cold stress or benign condition in the populations of Drosophila melanogaster selected for increased resistance to cold shock.We observed the significant up-regulation of Hsp22, Hsp23, Hsp40, Hsp68, and Fst genes in the FSB and FCB populations during the recovery phase post cold shock compared to the no shock condition. However, there was not a significant change in the transcript levels of these genes between FSB and FCB under both the cold stress or no shock condition. Additionally, we noticed higher total lipid levels in the females from cold shock treatment than those from no shock treatment. This finding suggests that cold selected populations have different mechanisms to sustain cold stress.
TP63-TRIM29 axis regulate enhancer methylation and chromosomal instability in prostate cancer
Authors: Sultanov R. , Mulyukina A. , Zubkova O. , Fedoseeva A. , Bogomazova A. , Klimina K. , Larin A. , Zatsepin T. , Prikazchikova T. , Sharova E. , Generozov E. , Govorun V. , Lagarkova M. , Arapidi G. 
Published: March 2022

AbstractProstate adenocarcinoma (PRAD) is the second most common cause of cancer-related deaths in men. PRAD is often characterized by DNA methylation variability and a high rate of large genomic rearrangements. To elucidate the reasons behind such high variance, we used weighted gene co-expression network analysis for integration RNA-seq, DNA methylation and copy number alterations data from The Cancer Genome Atlas PRAD. Our results show that only a single cluster of co-expressed genes is associated with genomic and epigenomic instability. Within this cluster, TP63 and TRIM29 are key transcription regulators. We revealed that TP63 regulates the level of enhancer methylation in prostate basal epithelium cells. TRIM29 forms a complex with TP63 and together regulate the expression of genes specific to the prostate basal epithelium. Moreover, TRIM29 binds DNA repair proteins and prevents formation of the TMPRSS2:ERG gene fusion typically observed in PRAD. Therefore, the study shows that TRIM29 and TP63 are important regulators maintaining the identity of the basal epithelium under physiological conditions. Finally, we uncover the role of TRIM29 in PRAD development.
Ketones facilitate transcriptional resolution of secondary DNA structures in premature aging
Authors: Petr Michael Angelo , Carmona-Marin Lina M , Tulika Tulika , Kristensen Stella , Reves Simon , Bakula Daniela , Keijzers Guido , Osborne Brenna , Mitchell Sarah J , Hamilton Sam , Kato Jonathan , Alfaras Irene , Teklu Amanuel A. , Heckenbach Indra , Madsen Jakob , Ezra Michael Ben , Mkrtchyan Garik , Varner Erika , Fink Benjamin , Krusenstiern Eliana von , Snyder Nathaniel W , Herranz Hector , Cabo Rafael de , Scheibye-Knudsen Morten 
Published: March 2022

SUMMARYThere is currently no established intervention for Cockayne syndrome, a disease characterized by progressive early onset neurodegeneration with features of premature aging. Here, we tested if acetyl-CoA precursors, citrate and beta-hydroxybutyrate, could reduce features of Cockayne syndrome in three model systems. We identified the gene Helicase 89B as a homologue of CSB in drosophila and found that the ketone beta-hydroxybutyrate rescued features of premature aging in Hel89B deficient flies. In mammals, loss of the citrate carrier Indy exacerbated the phenotype of Csbm/m mice which was rescued by a ketogenic diet. The rescue effect appeared to be mediated through ketone stimulated histone acetylation and facilitation of transcriptional readthrough of secondary DNA structures. These findings link a ketogenic diet with transcriptional resolution of secondary structures and DNA repair.
Identifying commonalities between cell lines and tumors at the single cell level using Sobolev Alignment of deep generative models
Authors: Mourragui Soufiane M.C. , Siefert Joseph C. , Reinders Marcel J.T. , Loog Marco , Wessels Lodewyk F.A. 
Published: March 2022

AbstractPreclinical models are essential to cancer research, however, key biological differences with patient tumors result in reduced translatability to the clinic and high attrition rates in drug development. Variability among and between patients, preclinical models, and individual cells obscures commonalities which could otherwise be exploited therapeutically. To discover the shared biological processes between cell line models and clinical tumors we developedSobolev Alignment, a computational framework which uses deep generative models to capture non-linear processes in single-cell RNA sequencing data and kernel methods to align and interpret these processes. We show that our approach faithfully captures shared processes on a set of three synthetic datasets. Exploiting two large panels of untreated non-small cell lung cancer cell lines and patients, we identify the similarities between cell lines and tumors and show the conservation of key mitotic and immune-related pathways. Employing our approach on a large in-vitro perturbation screen, we show that processes captured by our method faithfully recapitulate the known modes of action of clinically approved drugs and allow investigation into the mode of action of an uncharacterized drug.
Experience does not change the importance of wind support for migratory route selection by a soaring bird
Authors: Brønnvik Hester , Safi Kamran , Vansteelant Wouter M. G. , Byholm Patrik , Nourani Elham 
Published: March 2022

AbstractMigration is a complex behavior that is costly in terms of time, energy, and risk of mortality. Thermal soaring birds rely on airflow, specifically wind support and uplift, to offset their energetic costs of flight. Their migratory routes are a record of movement decisions to negotiate the atmospheric environment and achieve efficiency. Because thermal soaring is a complex flight type that young birds need to learn, we expected that, as individuals gain more experience, their movement decisions will also increasingly favor the best thermal uplift conditions. We quantified how route choice during autumn migration of young European honey buzzards (Pernis apivorus) was adjusted to wind support and uplift over up to four years of migration and compared this to the choices of adult birds. We found that wind support was important in all migrations. However, we did not find an increase in the use of thermal uplifts, which could be an artifact of the uplift proxies that we used. Age-specific variations in response to airflow might occur at a smaller spatio-temporal scale than we investigated.
Integrative analysis of genomic and transcriptomic alterations of AGR2 and AGR3 in cancer
Authors: Fessart Delphine , Villamor Ines , Chevet Eric , Delom Frederic , Robert Jacques 
Published: March 2022

AbstractThe AGR2 and AGR3 genes have been shown by numerous groups to be functionally associated to adenocarcinoma progression and metastasis. We explore in this paper the data available in databases concerning genomic and transcriptomic features concerning these two genes: the NCBI dbSNP database was used to explore the presence and roles of constitutional SNPs, and the NCI, CCLE and TCGA databases were used to explore somatic mutations and copy number variations (CNVs), as well as mRNA expression of these genes in human cancer cell lines and tumours. Relationships of AGR2/3 expression with whole genome mRNA expression and cancer features (i.e. mutations and CNVs of oncogenes and tumour suppressor genes [TSG]) were established using CCLE and TCGA databases. In addition, the CCLE data concerning CRISPR gene extinction screens (Achilles project) were explored concerning these two genes and a panel of oncogenes and TSG. We observed that no functional polymorphism or recurrent mutation could be detected in AGR2 or AGR3. The expression of these genes was positively correlated with the expression of epithelial genes and inversely correlated with that of mesenchymal genes. It was also significantly associated with several cancer features, such as TP53 or SMAD4 mutations, depending on the gene and the cancer type. The CRISPR screens revealed in addition the absence of cell fitness modification upon gene extinction, in contrast to oncogenes (cell fitness decrease) and TSG (cell fitness increase). Overall, these explorations revealed that AGR2 and AGR3 proteins appear as common non-genetic evolutionary factors in the process of human tumorigenesis.
How does the mode of evolutionary divergence affect reproductive isolation?
Authors: De Sanctis Bianca , Schneemann Hilde , Welch John J. 
Published: March 2022

AbstractWhen divergent populations interbreed, the outcome will be affected by the genomic and phenotypic differences that they have accumulated. In this way, the mode of evolutionary divergence between populations may have predictable consequences for the fitness of their hybrids, and so for the progress of speciation. To investigate these connections, we present a new analysis of hybridization under Fisher’s geometric model, making few assumptions about the allelic effects that differentiate the hybridizing populations. Results show that the strength and form of postzygotic reproductive isolation (RI) depend on just two properties of the evolutionary changes, which we call the “total amount” and “net effect” of change, and whose difference quantifies the similarity of the changes at different loci, or their tendency to act in the same phenotypic direction. It follows from our results that identical patterns of RI can arise in different ways, since different evolutionary histories can lead to the same total amount and net effect of change. Nevertheless, we show how these estimable quantities do contain some information about the history of divergence, and that – thanks to Haldane’s Sieve – the dominance and additive effects contain complementary information.Impact SummaryWhen populations of animals or plants evolve differences in their genomes or traits, the nature of the differences will help to determine whether they can continue to interbreed. For example, the hybrid offspring may be infertile, or unlikely to survive to reproductive age, meaning that the two populations remain distinct from one another even after mating. However, in some cases the hybrids may be more fertile than their parents or have some other reproductive advantage. In this study, we use a mathematical model to relate hybrid fitness to the evolved differences separating the parents. We find that the outcome depends on just two properties of these differences, which capture the “total amount” and the “net effect” of evolutionary change. We then show that different evolutionary divergence scenarios or modes can lead to the exact same hybrid fitness. On the other hand, we can still make some inferences about the history of divergence by observing certain properties of hybrid fitness. Determining the relationship between hybrid fitness and the mode of evolutionary divergence will help to understand how new species form, to plan conservation interventions such as moving individuals between isolated populations to increase their adaptive potential, and to understand how existing species might interact when their habitats overlap, for example due to climate change or other human impacts.
Identification of genetic loci in lettuce mediating quantitative resistance to fungal pathogens
Authors: Pink Harry , Talbot Adam , Graceson Abi , Graham Juliane , Higgins Gill , Taylor Andrew , Jackson Alison C. , Truco Maria , Michelmore Richard , Yao Chenyi , Gawthrop Frances , Pink David , Hand Paul , Clarkson John P. , Denby Katherine 
Published: March 2022

AbstractLactuca sativaL. (lettuce) is an important leafy vegetable crop grown and consumed globally. Chemicals are routinely used to control major pathogens, including the causal agents of grey mould (Botrytis cinerea) and lettuce drop (Sclerotinia sclerotiorum). With increasing prevalence of pathogen resistance to fungicides and environmental concerns, there is an urgent need to identify sources of genetic resistance toB. cinereaandS. sclerotiorumin lettuce. We demonstrated genetic variation for quantitative resistance toB. cinereaandS. sclerotiorumin a set of 97 diverse lettuce and wild relative accessions, and between the parents of lettuce mapping populations. Transcriptome profiling across multiple lettuce accessions enabled us to identify genes with expression correlated with resistance, predicting the importance of post-transcriptional gene regulation in the lettuce defence response. We identified five genetic loci influencing quantitative resistance in a F10 mapping population derived from aLactuca serriola(wild relative) x lettuce cross, which each explained 5–10% of the variation. Differential gene expression analysis between the parent lines, and integration of data on correlation of gene expression and resistance in the diversity set, highlighted potential causal genes underlying the quantitative trait loci.Key MessageWe demonstrate genetic variation for quantitative resistance against important fungal pathogens in lettuce and its wild relatives, map loci conferring resistance and predict key molecular mechanisms using transcriptome profiling.
Not optimal, just noisy: the geometry of correlated variability leads to highly suboptimal sensory coding
Authors: Livezey Jesse A. , Sachdeva Pratik S. , Dougherty Maximilian E. , Summers Mathew T. , Bouchard Kristofer E. 
Published: March 2022

AbstractThe brain represents the world through the activity of neural populations. Correlated variability across simultaneously recorded neurons (noise correlations) has been observed across cortical areas and experimental paradigms. Many studies have shown that correlated variability improves stimulus coding compared to a null model with no correlations. However, such results do not shed light on whether neural populations’ correlated variability achieves optimal coding. Here, we assess optimality of noise correlations in diverse datasets by developing two novel null models each with a unique biological interpretation: a uniform correlations null model and a factor analysis null model. We show that across datasets, the correlated variability in neural populations leads to highly suboptimal coding performance according to these null models. We demonstrate that biological constraints prevent many subsets of the neural populations from achieving optimality according to these null models, and that subselecting based on biological criteria leaves coding performance suboptimal. Finally, we show that the optimal subpopulation is exponentially small as a function of neural dimensionality. Together, these results show that the geometry of correlated variability leads to highly suboptimal sensory coding.
Lag-optimized BOLD cerebrovascular reactivity derived from breathing task data has a stronger relationship with baseline cerebral blood flow
Authors: Stickland Rachael C. , Zvolanek Kristina M. , Moia Stefano , Caballero-Gaudes César , Bright Molly G. 
Published: March 2022

AbstractCerebrovascular reactivity (CVR) is an important indicator of cerebrovascular health and is commonly studied with the Blood Oxygenation Level Dependent functional MRI (BOLD-fMRI) response to a vasoactive stimulus. There is theoretical and empirical evidence to suggest that baseline cerebral blood flow (CBF) modulates the BOLD signal amplitude, and that baseline CBF may influence BOLD-CVR estimates. We address how some pertinent data acquisition and modelling choices affect the relationship between baseline CBF and BOLD-CVR: whether BOLD-CVR is modelled with breathing task data or just resting-state data, and whether BOLD-CVR amplitudes are optimized for hemodynamic lag effects. For the relationship between baseline CBF and BOLD-CVR, we assessed both between-subject correlations of average GM values and within-subject spatial correlations across cortical regions. Our results suggest that a simple breathing task addition to a resting-state scan, alongside lag-optimization within BOLD-CVR modelling, can improve BOLD-CVR correlations with baseline CBF, both between- and within-subjects, likely because these CVR estimates are more physiologically accurate. We report positive coupling between baseline CBF and BOLD-CVR, both between and within subjects; the physiological explanation of this positive coupling is unclear, and future research with larger sample sizes and more tightly controlled vasoactive stimuli is needed. Understanding how baseline vascular physiology relates to dynamic cerebrovascular processes will bring further insights into what drives between and within subject participant variability in BOLD-CVR measurements and related measurements of cerebrovascular function. These insights are particularly relevant when interpreting results in populations with altered vascular and/or metabolic baselines or impaired cerebrovascular reserve.
Heritable variation in thermoregulation is associated with reproductive success in the world’s largest bird
Authors: Svensson Erik I. , Schou Mads F. , Melgar Julian , Waller John , Engelbrecht Anel , Brand Zanell , Cloete Schalk , Cornwallis Charlie K. 
Published: March 2022

AbstractOrganisms inhabiting extreme thermal environments, such as desert birds, have evolved spectacular adaptations to thermoregulate during hot and cold conditions. However, our knowledge of selection for thermoregulation and the potential for evolutionary responses is limited, particularly for large organisms experiencing extreme temperature fluctuations. Here we use thermal imaging to quantify selection and genetic variation in thermoregulation in ostriches (Struthio camelus), the world’s largest bird species that is experiencing increasingly volatile temperatures. We found that females that are better at regulating their head temperatures (‘thermoregulatory capacity’) had higher egg-laying rates under hotter conditions. Thermoregulatory capacity was both heritable and showed signatures of local adaptation: females originating from more unpredictable climates were better at regulating their head temperatures in response to temperature fluctuations. Together these results reveal that past and present evolutionary processes have shaped genetic variation in thermoregulatory capacity, which appears to protect critical organs, such as the brain, from extreme temperatures during reproduction.Impact SummaryLarge animals inhabiting extreme thermal environments, such as deserts, are predicted to be particularly vulnerable to the increasing temperature fluctuations expected in the future. However, previous work on the evolutionary potential of thermoregulation has primarily focused on the effect of hot temperatures on the survival of small ectotherms. We know little about how large endothermic vertebrates, such as birds, will respond to changing temperatures. Here we study the ostrich (Struthio camelus), the world’s largest bird, that inhabits some of the hottest and driest regions on Earth. We show that the ability of females to reproduce during hot conditions is associated with the regulation of their head temperatures (‘thermoregulatory capacity’). Furthermore, variation in thermoregulation is heritable and related to past climatic conditions: females originating from parts of Africa with more extreme temperature fluctuations were better able to thermoregulate, indicating local adaptation to different climatic conditions. Together, these results suggest that thermoregulation in this large desert bird has evolved in response to past climatic conditions, remains genetically variable and is currently under selection through its effect on reproduction.
Tissue-Restricted Inhibition of mTOR Using Chemical Genetics
Authors: Wassarman Douglas R. , Bankapalli Kondalarao , Pallanck Leo J. , Shokat Kevan M. 
Published: March 2022

AbstractmTOR is a highly conserved eukaryotic protein kinase that coordinates cell growth and metabolism and plays a critical role in cancer, immunity, and aging. It remains unclear how mTOR signaling in individual tissues contributes to whole-organism processes because mTOR inhibitors, like the natural product Rapamycin, are administered systemically and target multiple tissues simultaneously. We developed a chemical-genetic system, termed selecTOR, that restricts the activity of a Rapamycin analog to specific cell populations through targeted expression of a mutant FKBP12 protein. This analog has reduced affinity for its obligate binding partner FKBP12, which reduces its ability to inhibit mTOR in wild-type cells and tissues. Expression of the mutant FKBP12, which contains an expanded binding pocket, rescues the activity of this Rapamycin analog. Using this system, we show that selective mTOR inhibition can be achieved in S. cerevisiae and human cells, and we validate the utility of our system in an intact metazoan model organism by identifying the tissues responsible for a Rapamycin-induced developmental delay in Drosophila.Significance StatementmTOR plays a number of critical organismal roles, including in cell growth, development, immunity and aging, but dissecting the tissue-specific influences of mTOR has proven challenging. This work describes a simple system for identifying the specific tissues and cells responsible for the diverse functions of mTOR, and we show that our system can be used in organisms ranging from yeast to humans.