Oxygen Sensing in Drosophila: Multiple Isoforms of the Prolyl Hydroxylase Fatiga Have Different Capacity to Regulate HIFα/Sima

Background: The Hypoxia Inducible Factor (HIF) mediates cellular adaptations to low oxygen. Prolyl-4-hydroxylases are oxygen sensors that hydroxylate the HIF alpha-subunit, promoting its proteasomal degradation in normoxia. Three HIFprolyl hydroxylases, encoded by independent genes, PHD1, PHD2, and PHD3, occur in mammals. PHD2, the longest PHD isoform includes a MYND domain, whose biochemical function is unclear. PHD2 and PHD3 genes are induced in hypoxia to shut down HIF dependent transcription upon reoxygenation, while expression of PHD1 is oxygen-independent. The physiologic significance of the diversity of the PHD oxygen sensors is intriguing. Methodology and Principal Findings: We have analyzed the Drosophila PHD locus, fatiga, which encodes 3 isoforms, FgaA, FgaB and FgaC that are originated through a combination of alternative initiation of transcription and alternative splicing. FgaA includes a MYND domain and is homologous to PHD2, while FgaB and FgaC are shorter isoforms most similar to PHD3. Through a combination of genetic experiments in vivo and molecular analyses in cell culture, we show that fgaB but not fgaA is induced in hypoxia, in a Sima-dependent manner, through a HIF-Responsive Element localized in the first intron of fgaA. The regulatory capacity of FgaB is stronger than that of FgaA, as complete reversion of fga loss-of-function phenotypes is observed upon transgenic expression of the former, and only partial rescue occurs after expression of the latter. Conclusions and Significance: Diversity of PHD isoforms is a conserved feature in evolution. As in mammals, there are hypoxia-inducible and non-inducible Drosophila PHDs, and a fly isoform including a MYND domain co-exists with isoforms lacking this domain. Our results suggest that the isoform devoid of a MYND domain has stronger regulatory capacity than that including this domain.Fil:Acevedo, J.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Centanin, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Dekanty, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Wappner, P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Microvertebrates preserved in mammal burrows from the Holocene of the Argentine Pampas: a taphonomic and paleoecological approach

Microvertebrates are a major component of many assemblages recovered from the Quaternary of the Argentine Pampas. The main goal of this paper is to analyse the taphonomic history of a Holocene microfossil bonebed, recovered from the infilling of a burrow. Evidences suggest the plains vizcacha Lagostomus maximus as the putative producer of the burrow. The assemblage includes individuals belonging to different taxa of mammals (marsupials and rodents) and reptiles (snakes). Taphonomic features suggest that the accumulation inside the burrow was related to flooding processes in the plain. The burrow was a natural trap that favoured the accumulation and preservation of remains corresponding to individuals from different sources. According to the taphonomic evidence, some individuals (Lagostomus maximus, Lestodelphys halli and Serpentes indet.) died inside the burrow, whereas others (Microcavia australis, Reithrodon auritus and Ctenomys sp.) died outside the burrow, and after a time of being exposed on the surface their remains were transported by surface run-offs into the burrow. The record of Lestodelphys halli and Serpentes indet. in the burrow produced by Lagostomus maximus could be related to a circumstantial use. Mammal burrows are a significant taphonomic mode for the late Cenozoic of the Argentine Pampas

Drosophila Genome-Wide RNAi Screen Identifies Multiple Regulators of HIF–Dependent Transcription in Hypoxia

Hypoxia-inducible factors (HIFs) are a family of evolutionary conserved alpha-beta heterodimeric transcription factors that induce a wide range of genes in response to low oxygen tension. Molecular mechanisms that mediate oxygen-dependent HIF regulation operate at the level of the alpha subunit, controlling protein stability, subcellular localization, and transcriptional coactivator recruitment. We have conducted an unbiased genome-wide RNA interference (RNAi) screen in Drosophila cells aimed to the identification of genes required for HIF activity. After 3 rounds of selection, 30 genes emerged as critical HIF regulators in hypoxia, most of which had not been previously associated with HIF biology. The list of genes includes components of chromatin remodeling complexes, transcription elongation factors, and translational regulators. One remarkable hit was the argonaute 1 (ago1) gene, a central element of the microRNA (miRNA) translational silencing machinery. Further studies confirmed the physiological role of the miRNA machinery in HIF–dependent transcription. This study reveals the occurrence of novel mechanisms of HIF regulation, which might contribute to developing novel strategies for therapeutic intervention of HIF–related pathologies, including heart attack, cancer, and stroke

Network analysis of sea turtle movements and connectivity: A tool for conservation prioritization

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: The data that support the findings of this study are available in the Supplementary Material of this article and Zenodo (https://doi.org/10.5281/zenodo.5898578). Details for all animals included in this study are provided in Appendices S1 and S2. Data used to create the spatial networks are listed in the Appendices S3 and S4. The geospatial files for all networks are available on the Migratory Connectivity in the Ocean Project website (https://mico.eco) and Dryad (https://doi.org/10.5061/dryad.j3tx95xg9). Additional data that support the findings of this study are available from the corresponding author upon reasonable request.Aim Understanding the spatial ecology of animal movements is a critical element in conserving long-lived, highly mobile marine species. Analyzing networks developed from movements of six sea turtle species reveals marine connectivity and can help prioritize conservation efforts. Location Global. Methods We collated telemetry data from 1235 individuals and reviewed the literature to determine our dataset's representativeness. We used the telemetry data to develop spatial networks at different scales to examine areas, connections, and their geographic arrangement. We used graph theory metrics to compare networks across regions and species and to identify the role of important areas and connections. Results Relevant literature and citations for data used in this study had very little overlap. Network analysis showed that sampling effort influenced network structure, and the arrangement of areas and connections for most networks was complex. However, important areas and connections identified by graph theory metrics can be different than areas of high data density. For the global network, marine regions in the Mediterranean had high closeness, while links with high betweenness among marine regions in the South Atlantic were critical for maintaining connectivity. Comparisons among species-specific networks showed that functional connectivity was related to movement ecology, resulting in networks composed of different areas and links. Main conclusions Network analysis identified the structure and functional connectivity of the sea turtles in our sample at multiple scales. These network characteristics could help guide the coordination of management strategies for wide-ranging animals throughout their geographic extent. Most networks had complex structures that can contribute to greater robustness but may be more difficult to manage changes when compared to simpler forms. Area-based conservation measures would benefit sea turtle populations when directed toward areas with high closeness dominating network function. Promoting seascape connectivity of links with high betweenness would decrease network vulnerability.International Climate Initiative (IKI)German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU

Complexities of Assessing the Disease Burden Attributable to Leishmaniasis

Among parasitic diseases, morbidity and mortality caused by leishmaniasis are surpassed only by malaria and lymphatic filariasis. However, estimation of the leishmaniasis disease burden is challenging, due to clinical and epidemiological diversity, marked geographic clustering, and lack of reliable data on incidence, duration, and impact of the various disease syndromes. Non-health effects such as impoverishment, disfigurement, and stigma add to the burden, and introduce further complexities. Leishmaniasis occurs globally, but has disproportionate impact in the Horn of Africa, South Asia and Brazil (for visceral leishmaniasis), and Latin America, Central Asia, and southwestern Asia (for cutaneous leishmaniasis). Disease characteristics and challenges for control are reviewed for each of these foci. We recommend review of reliable secondary data sources and collection of baseline active survey data to improve current disease burden estimates, plus the improvement or establishment of effective surveillance systems to monitor the impact of control efforts

Ecological phytochemistry of Cerrado (Brazilian savanna) plants

The Cerrado (the Brazilian savanna) is one of the vegetation formations of great biodiversity in Brazil and it has experienced strong deforestation and fragmentation. The Cerrado must contain at least 12,000 higher plant species.We discuss the ecological relevance of phytochemical studies carried out on plants from the Cerrado, including examples of phytotoxicity, antifungal, insecticidal and antibacterial activities. The results have been classified according to activity and plant family. The most active compounds have been highlighted and other activities are discussed. A large number of complex biochemical interactions occur in this system. However, only a small fraction of the species has been studied from the phytochemical viewpoint to identify the metabolites responsible for these interactions