Biology subjects

Ylla, G.

Publications and source records attributed to Ylla, G..

17 recordsLinked to original sources

bioRxiv2026

miR-378a Controls Cardiomyocyte Metabolism and Angiogenic Signaling

AimsWhile the muscle-enriched microRNA-378a (miR-378a) has been implicated in cardiac hypertrophy and stress responses, its role in maintaining cardiomyocyte metabolic homeostasis, mitochondrial function, and angiogenic paracrine signaling under physiological and post-injury conditions remains unclear. This study addresses these gaps by examining the molecular and functional consequences of miR-378a deficiency in murine heart and human cardiomyocytes. Methods and ResultsCardiac structure and function were analyzed in miR-378a-deficient (miR-378a-/-) and wild-type (miR-378a+/+) mice at 12 weeks and 17 months of age, revealing that miR-378a loss promoted myocardial fibrosis, altered IGF1R-AKT signaling, and impaired cardiac performance, with age-dependent effects. Integrated transcriptomic and proteomic analyses in miR-378a-/- and control mice, as well as in human iPSC-derived cardiomyocytes (hiPSC-CM) of both genotypes, revealed deregulated pathways related to translation, metabolism, and cardiomyopathy-associated signaling. In hiPSC-CM, miR-378a knockout (KO) impaired mitochondrial respiration, disrupted mitochondrial morphology, and reduced mitochondrial DNA content, accompanied by altered mitophagy and biogenesis. KO cells also showed increased glucose uptake but reduced glycogen storage, accompanied by changes in key metabolic regulators, and displayed diminished angiogenic potential. Finally, hiPSC-CM overexpressing miR-378a were delivered in a mouse model of acute myocardial infarction, but overexpression did not further enhance their therapeutic effect. ConclusionsThis study broadens our understanding of miR-378as physiological role in murine hearts and human cardiomyocytes, demonstrating its impact on contractility, mitochondrial integrity, glucose metabolism, and angiogenic paracrine signaling. However, overexpression of miR-378a in hiPSC-CM offers limited additional benefit in cell therapy for acute myocardial infarction.

cell biology↗

bioRxiv2026

The dynamics of piRNA expression in Blattella germanica ovaries

The cockroach Blattella germanica possesses panoistic ovaries, in which oocytes lack nurse cells and therefore need to rely on their own transcriptional activity to support embryogenesis. Ovarian development in this species involves the development of a single basal ovarian follicle (BOF) per gonadotropic cycle, a process strictly regulated by endocrine signals, primarily juvenile hormone and ecdysone, which act at both the transcriptional and translational levels. In addition, transcriptional activity in these ovaries is necessary for both regulating and genome protection, and at this level, PIWI-interacting RNAs (piRNAs) play an essential role. Although insect ovaries are known to be particularly rich in piRNAs, their function in ovary maturation is still not well defined. For this purpose, we characterize the piRNA expression dynamics across seven key developmental and reproductive stages, ranging from late nymphal instars to post-vitellogenic adults. piRNA expression in B. germanica shows coordinated fluctuations. Expression remains stable in previtellogenic ovaries, whereas vitellogenic ovaries show pronounced changes. Moreover, vitellogenic ovaries exhibit reduced piRNA diversity due to strong enrichment of a subset of highly expressed piRNAs. Our data show that although piRNAs predominantly map to transposable elements, particularly LINEs, there is a notable increase in gene-derived piRNAs toward the end of the cycle. Our results suggest regulatory roles of piRNAs in modulating both TEs and mRNAs during BOF maturation, likely related to changes in the follicular cell program.

developmental biology↗

bioRxiv2025

Social media posts as a source of ecological information over time: using Twitter (X) as a proof of principle

Acquiring data about ecology over long periods of time and large geographical areas is often difficult, expensive, and takes a long time. Here, we explore whether, through millions of daily posts on social networks, we could be constantly and unconsciously accumulating data regarding important biological patterns over the years. Data analysis from generalist social networks has been successfully applied in different research fields, most notably in political science and epidemiology. Here, we evaluate their potential and drawbacks for studying biological patterns of other organisms over time. To that end, we used millions of posts on Twitter (currently X), over 11 years, on four different insect groups: cockroaches, crickets, Monarch butterflies, and mosquitoes. Our results show that through millions of daily tweets, we could identify temporal periodic patterns that reflect their unique known phenology of the four insect taxa studied. Given the 11-year span of the dataset, we could also track changes in their patterns over the years that might be related to environmental factors. Using a sentiment analysis, we could also characterize the emotions of people towards these animals, which is important for the design of awareness campaigns. We also discuss the limitations of these data, such as the potential that social media data might have for spatial tracking of migrations. In summary, we show compelling evidence for the use of social network data for biologists and provide a theoretical and practical framework for exploring these sources of data.

ecology↗

bioRxiv2025

Chromosome-scale genome assembly and annotation of the two-spotted cricket Gryllus bimaculatus (Orthoptera: Gryllidae)

The two-spotted cricket, Gryllus bimaculatus, is a key hemimetabolous model organism for developmental biology, neuroscience, and regeneration. The existing reference genome is, however, highly fragmented into 47,877 scaffolds, hampering chromosome-scale analyses for these fields. Here, we report a high-quality, chromosome-scale genome assembly for the white-eyed mutant strain of this cricket, generated using a combination of Nanopore and PacBio HiFi long reads, integrated with Hi-C data. The final 1.62 Gbp assembly achieves a scaffold N50 of 107.4 Mbp, a significant improvement in contiguity over the previous 6.3 Mbp N50. We anchored 94.45% of the assembly into 15 pseudomolecules, consistent with the known karyotype (n = 15). The genome completeness (BUSCO v6.0.0 insecta_odb12) reached 98.1%. We also updated the annotation, identifying 14,964 protein-coding genes. This gene set shows markedly improved completeness (BUSCO v6.0.0 insecta_odb12: 95.7%) compared with the previous annotation (81.2%) and successfully recovers all nine essential neuropeptide genes previously reported as missing from the draft assembly. This chromosome-scale genomic resource provides an essential foundation for comparative and functional genomics in G. bimaculatus.

genomics↗

bioRxiv2025

piRAT: piRNA Annotation Tool for annotating, analyzing, and visualizing piRNAs

MotivationIn recent years, Piwi-interacting RNAs (piRNAs) have been found to be involved in different biological roles beyond their initially identified role of protecting the germline genome. However, there is a lack of robust computational tools that facilitate their accurate annotation, analysis, and visualization, which would allow large-scale analysis of piRNAs across samples and species. ResultsWe present piRAT, a piRNA Annotation Tool for annotating both primary piRNAs from piRNA clusters and secondary piRNAs generated via the ping-pong cycle, using small RNA-seq data mapped to a genome. piRAT also performs descriptive analyses and generates comprehensive reports with visualizations to support annotations and provide further insights. Availability and ImplementationpiRAT is available on GitHub (https://github.com/ylla-lab/piRAT), implemented in Python 3, and released under MIT license. It is also installable through pip, conda, and available as Docker container (https://hub.docker.com/u/domrob). The Python implementation runs natively on Linux and in WSL in Windows, and the Docker image can run on Linux, Windows, and MacOS.

bioinformatics↗

bioRxiv2025

piRNAs are abundant in the early embryo of the crustacean Parhyale hawaiensis

PIWI-interacting RNAs (piRNAs) are a group of short ([~]21-31 nucleotide) non-coding RNAs that protect the germline of metazoans against the activity of genomic parasites known as transposable elements (TEs). Although originally discovered in Drosophila where they are germ-line restricted, recent studies in arthropods have shown piRNAs are often expressed also in somatic cells suggesting they might have originally evolved as a somatic immune system protecting against the detrimental action of TEs in the last common ancestor. Beyond their classic TE-silencing roles piRNAs functions range from sex determination in moths, to degradation of maternal mRNAs during the maternal-to-zygotic transition, thus highlighting the need for more sampling across the tree of life, particularly in underrepresented speciose rich subphyla such as the crustaceans were to date only two representatives have been analysed. In this study we sequenced and analysed putative piRNAs in the amphipod Parhyale hawaiensis, throughout a time-course of embryogenesis. Initially, during early embryogenesis piRNAs-mapping reads were abundant, maternally loaded piRNAs and showed the hallmark signatures of piRNA processing suggesting active targeting of TEs. Interestingly, this initial high content was followed by a dramatic loss of piRNA-mapping transcripts and signatures during mid-embryogenesis shortly after germ cell specification. This was confirmed by in-situ hybridization of key mRNAs coding for piRNA pathway proteins which revealed their expression becomes restricted specifically to the germ cells by early germband formation, providing an explanation for the observed reduction in piRNA abundance at later stages, and suggesting that piRNAs are absent in Parhyale post embryonic somatic cells.

developmental biology↗

bioRxiv2025

Chinmo is a novel regulator of differential Hippo signaling response within a single developing organ.

Orchestrated control of proliferation of multiple cell types is essential for building a healthy organ. Here we use larval ovary development in Drosophila melanogaster as a model to understand the homeostasis of somatic and germ line cells in the formation of the female adult reproductive organ. We previously showed that the highly conserved Hippo signaling pathway regulates proliferation of both germ line and somatic cells in the D. melanogaster larval ovary. Response to Hippo signaling appeared to be mediated by different genetic mechanisms in germ line and soma, but the mechanism allowing distinct responses to the same signaling pathway remained unknown. Here we perform cell type-specific RNA-Seq of isolated germ line and somatic cells from the developing ovary at multiple time points spanning the formation of germ line stem cell niches, in either a Hippo signaling loss- or gain-of-function genetic background. Applying network analysis to these data revealed a novel regulator of ovarian development, the transcription factor chinmo. Subsequent experimental validation showed that chinmo acts as a key germ cell-specific translator of Hippo signaling in the developing ovary, allowing the Hippo signal to be transduced in cell type-specific ways in germ line and somatic cells within the same organ.

developmental biology↗

bioRxiv2025

ERGA-BGE Reference Genome of Loboptera subterranea: a cave adapted cockroach endemic to the Canary Islands

Species of the genus Loboptera from the Canary Islands are adapted to life in subterranean environments, except Loboptera canariensis and Loboptera decipiens which inhabit epigean, often influenced by human activities. The genome of Loboptera subterranea provides a valuable resource for understanding the genetic basis of how the Canarian Loboptera species evolved and thrived in subterranean environments. A total of 14 contiguous chromosomal pseudomolecules were assembled from the genome sequence. This chromosome-level assembly encompasses 2.7 Gb, composed of 486 contigs and 90 scaffolds, with contig and scaffold N50 values of 13.1 Mb and 202.7 Mb, respectively.

genomics↗

bioRxiv2023

Two avian Plasmodium species trigger different transcriptional responses on their vector Culex pipiens

Malaria is a mosquito-borne disease caused by protozoans of the genus Plasmodium that affects both humans and wildlife. The fitness consequences of infections by avian malaria are well known in birds, however, little information exists on its impact on mosquitoes. Here we study how Culex pipiens mosquitoes transcriptionally respond to infection by two different Plasmodium species, P. relictum and P. cathemerium, differing in their virulence (mortality rate) and transmissibility (parasite presence in exposed mosquitoes saliva). We study the mosquito response to the infection at three critical stages of parasite development: formation of ookinetes at 24 hours post-infection (hpi), the release of sporozoites into the hemocoel at 10 days post-infection (dpi), and storage of sporozoites in the salivary glands at 21dpi. For each time point, we characterized the gene expression of mosquitoes infected with each P. relictum and P. cathemerium and mosquitoes fed on an uninfected bird and, subsequently, compared their transcriptomic responses. Differential gene expression analysis showed most of the transcriptomic changes occurred during the early infection stage (24 hpi), especially when comparing P. relictum and P. cathemerium infected mosquitoes. Differentially expressed genes in mosquitoes infected with each species were related mainly to the immune response, trypsin, and other serine-proteases metabolism. We conclude that these differences in response may partly play a role in the differential virulence and transmissibility previously observed in P. relictum and P. cathemerium in Cx. pipiens.

genomics↗

bioRxiv2022

oskar acts with the transcription factor Creb to regulate long-term memory in crickets

Novel genes have the potential to drive the evolution of new biological mechanisms, or to integrate into pre-existing regulatory circuits and contribute to the regulation of older, conserved biological functions. One such gene, the novel insect-specific gene oskar, was first identified based on its role in establishing the Drosophila melanogaster germ line. We previously showed that this gene likely arose through an unusual domain transfer event involving bacterial endosymbionts, and played a somatic role before evolving its well-known germ line function. Here, we provide empirical support for this hypothesis in the form of evidence for a novel neural role for oskar. We show that oskar is expressed in the adult neural stem cells of a hemimetabolous insect, the cricket Gryllus bimaculatus. In these stem cells, called neuroblasts, oskar is required together with the ancient animal transcription factor Creb to regulate long-term (but not short-term) olfactory memory. We provide evidence that oskar positively regulates Creb, which plays a conserved role in long-term memory across animals, and that oskar in turn may be a direct target of Creb. Together with previous reports of a role for oskar in nervous system development and function in crickets and flies, our results are consistent with the hypothesis that oskars original somatic role may have been in the insect nervous system. Moreover, its co-localization and functional cooperation with the conserved pluripotency gene piwi in the nervous system may have facilitated oskars later co-option to the germ line in holometabolous insects.

animal behavior and cognition↗

bioRxiv2022

Reduction of embryonic E93 expression as a key factor for the evolution of insect metamorphosis

The early embryo of the cockroach Blattella germanica exhibits high E93 expression. In general, E93 triggers adult morphogenesis during postembryonic development, but in the cockroach E93 is also crucial in early embryogenesis. Moreover, the embryonic levels of E93 expression are high in hemimetabolan insects, while in holometabolans they are very low. They are also low in Thysanoptera and in Hemiptera Sternorrhyncha with postembryonic quiescent stages, as well as in Odonata, the nymph of which is very different from the adult. In ametabolans, such as the Zygentoma Thermobia domestica, E93 expression levels are very high in the early embryo, whereas during postembryonic development they are medium and relatively constant. Given that embryogenesis of hemimetabolans yields an adultiform nymph, we speculate that E93 plays some sort of adult triggering role in the embryo of these species. We conjecture that the reduction of E93 transcript levels in the embryo has been instrumental in the evolution of insect metamorphosis. The suppression of E93 expression during the nymphal period, and its concentration in the preadult stage, is consubstantial with the emergence of hemimetaboly. As such, attenuation of E93 expression in the embryo could have resulted in a larval genetic program and the emergence of holometaboly. Independent decreases of E93 expression in the embryo of Odonata, Thysanoptera, and different groups of Hemiptera Sternorrhyncha would have allowed the development of modified juvenile stages adapted to specific ecophysiological conditions.

developmental biology↗

bioRxiv2021

Distinct gene expression dynamics in germ line and somatic tissue during ovariole morphogenesis in Drosophila melanogaster

The survival and evolution of a species is a function of the number of offspring it can produce. In insects the number of eggs that an ovary can produce is a major determinant of reproductive capacity. Insect ovaries are made up of tubular egg-producing subunits called ovarioles, whose number largely determines the number of eggs that can be potentially laid. Ovariole number is directly determined by the number of cellular structures called terminal filaments, which are stacks of cells that assemble in the larval ovary. Elucidating the developmental and regulatory mechanisms of terminal filament formation is thus key to understanding the regulation of insect reproduction through ovariole number regulation. We systematically measured mRNA expression of all cells in the larval ovary at the beginning, middle and end of terminal filament formation. We also separated somatic and germ line cells during these stages and assessed their tissue-specific gene expression during larval ovary development. We found that the number of differentially expressed somatic genes is highest during late stages of terminal filament formation and includes many signaling pathways that govern ovary development. We also show that germ line tissue, in contrast, shows greater differential expression during early stages of terminal filament formation, and highly expressed germ line genes at these stages largely control cell division and DNA repair. We provide a tissue-specific and temporal transcriptomic dataset of gene expression in the developing larval ovary as a resource to study insect reproduction.

developmental biology↗

bioRxiv2021

siRNA enrichment in Argonaute 2-depleted Blattella germanica

BackgroundRNA interference (RNAi) is a cellular mechanism used to fight various threats, including transposons, aberrant RNA, and some types of viruses. It relies on dsRNA detection and, through a mechanism involving Dicer-2 (Dcr-2) and Argonaute 2 (AGO2), together with a small RNA fragment (siRNA) as a complementary guide, binds to an RNA and cleaves it. MethodsUsing the cockroach Blattella germanica as a model, we examined AGO2 activity by depleting its mRNA levels using RNAi and analyzing the phenotypes produced. ResultsSilencing AGO2 expression had no remarkable effect on nymphal development or reproduction. dsRNA treatment triggered an immediate and transitory increase in AGO2 expression, independently of Dcr-2 action. In addition, we analyzed the siRNAs generated after injecting a heterologous dsRNA in control and AGO2-depleted animals. The results revealed that siRNAs were distributed non-uniformly along the dsRNA sequence. In AGO2-depleted animals, the proportion of 22 nucleotide reads was higher and accumulations of reads appeared in areas less well-represented in the controls. We also detected a slight preference for cytosine as the first nucleotide in controls to be lost in AGO2-depleted individuals. Conclusions/General significanceThe siRNAs produced from a dsRNA are heterogeneously distributed along the length of the dsRNA and this arrangement depends on the sequence. AGO2 exerts its role as nuclease on the siRNA duplexes independently of its action on the homologous mRNA. This study sheds light on an extremely useful process for reverse genetics in laboratories, in addition to the design of more effective, specific, and eco-friendly pest-control strategies. Highlights- RNA interference is used to fight cellular threats including transposons and viruses - Silencing AGO2 in Blattella germanica does not affect development or reproduction - siRNA distribution along the dsRNA sequence is non-uniform and sequence dependent - AGO2 depletion increased the proportion of 22 nt reads in certain areas

physiology↗

bioRxiv2020

DNA methylation in cockroaches is essential in early embryo development and reduces gene expression noise

The influence of DNA methylation on gene behavior, and its consequent phenotypic effects appear to be very important, but the details are not well understood. Insects offer a diversity of DNA methylation modes, making them an excellent lineage for comparative analyses. However, functional studies have tended to focus on quite specialized holometabolan species, such as wasps, bees, beetles, and flies. Here we have studied DNA methylation in a hemimetabolan insect, the cockroach Blattella germanica, a model of early-branching insects. In this cockroach, one of the main genes responsible for DNA methylation, DNA methyltransferase 1 (DNMT1), is expressed in early embryogenesis. In our experiments, DNMT1 interference by RNAi reduces DNA methylation and impairs blastoderm formation. Using Reduced Representation Bisulfite Sequencing (RRBS) and transcriptomic analyses, we observed that hypermethylated genes are associated with metabolism and are highly expressed, whereas hypomethylated genes are related to signaling and have low expression levels. Moreover, the expression change in hypermethylated genes is greter than that in hypomethylated genes, whereas hypermethylated genes have less expression variability than hypomethylated genes. The latter observation has also been reported for humans and in Arabidopsis plants. A reduction in expression noise may therefore be one of the few universal effects of DNA methylation.

developmental biology↗

bioRxiv2020

Cricket genomes: the genomes of future food

Most of our knowledge of insect genomes comes from Holometabolous species, which undergo the complete metamorphosis and have genomes under 2Gb with little signs of DNA methylation. In contrast, Hemiemetabolous insects undergo the ancestral incomplete metamorphosis and have larger genomes with high levels of DNA methylation. Hemimetabolous species from the Orthopteran order (grasshoppers and crickets) have some of the largest insect genomes. What drives the evolution of these unusual insect genome sizes, remains unknown. Here we report the sequencing, assembly and annotation of the 1.66-Gb genome of the Mediterranean field cricket Gryllus bimaculatus, and the annotation of the 1.60-Gb genome of the Hawaiian cricket Laupala kohalensis. We compare these two cricket genomes with those of 14 additional insects, and find evidence that hemimetabolous genomes expanded due to transposable element activity. Based on the ratio of observed to expected CpG sites, we find higher conservation and stronger purifying selection of methylated genes than non-methylated genes. Finally, our analysis suggests an expansion of the pickpocket class V gene family in crickets, which we speculate might play a role in the evolution of cricket courtship, including their characteristic chirping.

genomics↗

bioRxiv2018

Zelda and the evolution of insect metamorphosis

In the Endopterygote Drosophila melanogaster, Zelda is a key activator of the zygotic genome during the maternal-to-zygotic transition (MZT). Zelda binds cis-regulatory elements (TAGteam heptamers), and makes chromatin accessible for gene transcription. Recently, Zelda has been studied in two other Endopterygotes: Apis mellifera and Tribolium castaneum, and the Paraneopteran Rhodnius prolixus. We have studied Zelda in the cockroach Blattella germanica, a hemimetabolan, short germ-band, and Polyneopteran species. Zelda protein of B. germanica has the complete set of functional domains, which is typical of lower insects. The TAGteam heptamers of D. melanogaster have been found in the B. germanica genome, and the canonical one, CAGGTAG, is present at a similar relative number in the genome of these two species and in the genome of other insects, suggesting that, although within certain evolutionary constraints, the genome admits as many CAGGTAG motifs as its length allows. Zelda-depleted embryos of B. germanica show defects involving the blastoderm formation and the abdomen development and have genes contributing to these processes down-regulated. We conclude that in B. germanica Zelda strictly activates the zygotic genome, within the MZT, a role conserved in more derived Endopterygote insects. In B. germanica, Zelda is expressed during MZT, whereas in D. melanogaster and T. castaneum it is expressed well beyond this transition. Moreover, in these species and A. mellifera, Zelda has functions even in postembryonic development. The expansion of Zelda expression and functions beyond the MZT in holometabolan species might have been instrumental for the evolutionary transition from hemimetaboly to holometaboly. In particular, the expression of Zelda beyond the MZT during embryogenesis might have allowed building the morphologically divergent holometabolan larva.\n\nAuthor summaryIn early insect embryo development, the protein Zelda is a key activator of the zygotic genome during the maternal-to-zygotic transition. This has been thoroughly demonstrated in the fruit fly Drosophila melanogaster, as well as in the red flour beetle Tribolium castaneum, both species belonging to the most modified clade of endopterygote insects, showing complete (holometabolan) metamorphosis. In these species, Zelda is expressed and have functions in early embryogenesis, in late embryogenesis and in postembryonic stages. We have studied Zelda in the German cockroach, Blattella germanica, which belong to the less modified clade of polyneopteran insects, showing an incomplete (hemimetabolan) metamorphosis. In B. germanica, Zelda is significantly expressed in early embryogenesis, being a key activator of the zygotic genome during the maternal-to-zygotic transition, as in the fruit fly and the red flour beetle. Nevertheless, Zelda is not significantly expressed, and presumably has no functions, in late embryogenesis and in postembryonic stages of the cockroach. The data suggest that the ancestral function of Zelda in insects with hemimetabolan metamorphosis was to activate the zygotic genome, a function circumscribed to early embryogenesis. The expansion of Zelda expression and functions to late embryogenesis and postembryonic stages might have been a key step in the evolutionary transition from hemimetaboly to holometaboly. In hemimetabolan species embryogenesis produces a nymph displaying the essential adult body structure. In contrast, embryogenesis of holometabolan species produces a larva that is morphologically very divergent from the adult. Expression of Zelda in late embryogenesis might have been a key step in the evolution from hemimetaboly to holometaboly, since it would have allowed the building the morphologically divergent holometabolan larva.

evolutionary biology↗

bioRxiv2017

Hemimetabolous genomes reveal molecular basis of termite eusociality

Around 150 million years ago, eusocial termites evolved from within the cockroaches, 50 million years before eusocial Hymenoptera, such as bees and ants, appeared. Here, we report the first, 2GB genome of a cockroach, Blattella germanica, and the 1.3GB genome of the drywood termite, Cryptotermes secundus. We show evolutionary signatures of termite eusociality by comparing the genomes and transcriptomes of three termites and the cockroach against the background of 16 other eusocial and non-eusocial insects. Dramatic adaptive changes in genes underlying the production and perception of pheromones confirm the importance of chemical communication in the termites. These are accompanied by major changes in gene regulation and the molecular evolution of caste determination. Many of these results parallel molecular mechanisms of eusocial evolution in Hymenoptera. However, the specific solutions are remarkably different, thus revealing a striking case of convergence in one of the major evolutionary transitions in biological complexity.

evolutionary biology↗