Immunolocalization of a PIGR-like Protein in Tetrahymena thermophila

Netrins are pleiotropic signaling molecules which guide axonal development and help regulate processes such as angiogenesis. Netrins can act as chemorepellents for developing axons, and our previous work has shown that several netrins, including netrin-1, netrin-3, and netrin-4, are chemorepellents in Tetrahymena thermophila. In vertebrates, netrin-1 signals through several receptors, including those in the UNC-5 family. UNC-5 family proteins often signal through the src family of tyrosine kinases. We have previously characterized UNC-5 and src-like proteins in Tetrahymena, by immunolocalization and Western blotting. Sequencing of our src-like proteins gave a number of homologous sequences, including the sequence for polymeric immunoglobulin-like receptor (PIGR). With all of these findings in mind, we hypothesized that Tetrahymena might possess a receptor similar to PIGR, which would localize either to the plasma membrane or cilia of Tetrahymena

Biochemical Evidence for Netrin-Signaling Homologues in Tetrahymena thermophila

Netrins are pleiotropic guidance proteins that are involved in developmental signaling of branched structures within vertebrates. However, like many developmental pathways, dysregulation of the netrin pathway has been implicated in cancer progression and metastasis. Since Tetrahymena respond to guidance proteins, showing chemoattractant and chemorepellent behavior, we hypothesized that we could use these organisms as a model system for cancer signaling. We have previously found that netrin-1-peptided, netrin-3-peptide, and recombinant netrin-4 are all chemorepellents in this organism. Since netrin-1-peptide signals through a tyrosine kinase in Tetrahymena, we hypothesized that Tetrahymena might possess tyrosine kinases as well as a receptor homologous to UNC-5, a netrin receptor which relays signals via tyrosine kinases in vertebrates. Using immunoprecipitation with a polyclonal anti-UNC-5-B antibody, we purified a 250 kD protein from Tetrahymena whole cell extract. Similarly, we immunoprecipitated several proteins, including a 60 kD protein and a 75 kD protein using a polyclonal anti-src-antibody. Our purified samples were sent out for identification by mass spectroscopy. Mass spectroscopy indicated that we have purified a number of novel peptides not currently found in the Tetrahymena Genome Database. Our data indicate that the proteome database in this organism is incomplete, and that there are additional proteins waiting to be discovered in this organism

How the Western Was Won: Evidence for Netrin Signaling Machinery in Tetrahymena thermophila

Netrins are pleiotropic signaling molecules with diverse roles in animal development. Netrin signals through a number of receptors in animals, including the UNC-5 family, neogenin, DSCAM, and DCC. Previous studies have shown that netrin-1-peptide, netrin-3-peptide, and recombinant netrin-4 all act as chemorepellents in Tetrahymena (Kuruvilla et al., 2016, Khol et al., 2018; Bradley and Kuruvilla, 2020). In addition, netrin-1 peptide appears to signal through a tyrosine kinase in this organism (Kuruvilla et al., 2016), similar to vertebrate signaling through UNC-5, which uses the tyrosine kinase, src. In light of these data, we hypothesized that Tetrahymena thermophila possess netrin signaling machinery, including a tyrosine kinase. In order to investigate this hypothesis, we searched for various netrin receptors, as well as a src homologue, in Tetrahymena using immunofluorescence (Khol et al., 2018). We found that anti-UNC-5 and anti-neogenin antibodies showed fluorescence, while anti-DCC and anti-DSCAM antibodies did not. In addition, an anti-src antibody showed significant fluorescence in Tetrahymena (Khol et al., 2018. In our current study, we searched the Tetrahymena Genome Database for homologs of UNC-5, neogenin, and src. We also used Western blotting to screen for potential homologues of these proteins. At the present time, there are several proteins of interest which we would like to study further

Systematic challenges and opportunities in insect monitoring: a Global South perspective

Insect monitoring is pivotal for assessing biodiversity and informing conservation strategies. This study delves into the complex realm of insect monitoring in the Global South—world developing and least-developed countries as identified by the United Nations Conference on Trade and Development—highlighting challenges and proposing strategic solutions. An analysis of publications from 1990 to 2024 reveals an imbalance in research contributions between the Global North and South, highlighting disparities in entomological research and the scarcity of taxonomic expertise in the Global South. We discuss the socio-economic factors that exacerbate the issues, including funding disparities, challenges in collaboration, infrastructure deficits, information technology obstacles and the impact of local currency devaluation. In addition, we emphasize the crucial role of environmental factors in shaping insect diversity, particularly in tropical regions facing multiple challenges including climate change, urbanization, pollution and various anthropogenic activities. We also stress the need for entomologists to advocate for ecosystem services provided by insects in addressing environmental issues. To enhance monitoring capacity, we propose strategies such as community engagement, outreach programmes and cultural activities to instill biodiversity appreciation. Further, language inclusivity and social media use are emphasized for effective communication. More collaborations with Global North counterparts, particularly in areas of molecular biology and remote sensing, are suggested for technological advancements. In conclusion, advocating for these strategies—global collaborations, a diverse entomological community and the integration of transverse disciplines—aims to address challenges and foster inclusive, sustainable insect monitoring in the Global South, contributing significantly to biodiversity conservation and overall ecosystem health

Avifauna en dos complejos de páramo de Antioquia, Colombia

We characterized bird communities in two paramo complexes (Frontino-Urrao and Sonsón) in the department of Antioquia, Colombia, including the transition zones and the upper boundaries of cloud forests. We recorded 197 bird species (40 families), of which 7 presented some threat category, 1 is almost threatened, 5 are endemic, 15 near endemic, 4 boreal migratory species and 1 austral migratory species. We point out 12 species that are relevant, either due to their degree of national threat or because they represent geographic or altitudinal range extensions.Hicimos caracterizaciones rápidas de avifauna en dos complejos de páramo (Frontino-Urrao y Sonsón) en el departamento de Antioquia, Colombia, en el límite superior de bosques nublados, zonas de transición y páramos. Registramos 197 especies de aves (40 familias), de las cuales 7 presentan alguna categoría de amenaza, 1 está casi amenazada, 5 son endémicas, 15 casi endémicas, 4 son migratorias boreales y 1 es migratoria austral. Señalamos 12 especies de importancia, ya sea por su grado de amenaza nacional o por presentar ampliación en su rango de distribución geográfica o altitudinal

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

Sustainable care for children with cancer: a Lancet Oncology Commission.

We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020-50 would be four times greater than the cumulative treatment costs of$594 billion, producing a net benefit of $1986 billion on the global investment: a net return of$3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths

Copper-Triggered Aggregation of Ubiquitin

Neurodegenerative disorders share common features comprising aggregation of misfolded proteins, failure of the ubiquitin-proteasome system, and increased levels of metal ions in the brain. Protein aggregates within affected cells often contain ubiquitin, however no report has focused on the aggregation propensity of this protein. Recently it was shown that copper, differently from zinc, nickel, aluminum, or cadmium, compromises ubiquitin stability and binds to the N-terminus with 0.1 micromolar affinity. This paper addresses the role of copper upon ubiquitin aggregation. In water, incubation with Cu(II) leads to formation of spherical particles that can progress from dimers to larger conglomerates. These spherical oligomers are SDS-resistant and are destroyed upon Cu(II) chelation or reduction to Cu(I). In water/trifluoroethanol (80∶20, v/v), a mimic of the local decrease in dielectric constant experienced in proximity to a membrane surface, ubiquitin incubation with Cu(II) causes time-dependent changes in circular dichroism and Fourier-transform infrared spectra, indicative of increasing β-sheet content. Analysis by atomic force and transmission electron microscopy reveals, in the given order, formation of spherical particles consistent with the size of early oligomers detected by gel electrophoresis, clustering of these particles in straight and curved chains, formation of ring structures, growth of trigonal branches from the rings, coalescence of the trigonal branched structures in a network. Notably, none of these ubiquitin aggregates was positive to tests for amyloid and Cu(II) chelation or reduction produced aggregate disassembly. The early formed Cu(II)-stabilized spherical oligomers, when reconstituted in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes and in POPC planar bilayers, form annular and pore-like structures, respectively, which are common to several neurodegenerative disorders including Parkinson's, Alzheimer's, amyotrophic lateral sclerosis, and prion diseases, and have been proposed to be the primary toxic species. Susceptibility to aggregation of ubiquitin, as it emerges from the present study, may represent a potential risk factor for disease onset or progression while cells attempt to tag and process toxic substrates

A Genome-Wide Association Scan on the Levels of Markers of Inflammation in Sardinians Reveals Associations That Underpin Its Complex Regulation

Identifying the genes that influence levels of pro-inflammatory molecules can help to elucidate the mechanisms underlying this process. We first conducted a two-stage genome-wide association scan (GWAS) for the key inflammatory biomarkers Interleukin-6 (IL-6), the general measure of inflammation erythrocyte sedimentation rate (ESR), monocyte chemotactic protein-1 (MCP-1), and high-sensitivity C-reactive protein (hsCRP) in a large cohort of individuals from the founder population of Sardinia. By analysing 731,213 autosomal or X chromosome SNPs and an additional ∼1.9 million imputed variants in 4,694 individuals, we identified several SNPs associated with the selected quantitative trait loci (QTLs) and replicated all the top signals in an independent sample of 1,392 individuals from the same population. Next, to increase power to detect and resolve associations, we further genotyped the whole cohort (6,145 individuals) for 293,875 variants included on the ImmunoChip and MetaboChip custom arrays. Overall, our combined approach led to the identification of 9 genome-wide significant novel independent signals—5 of which were identified only with the custom arrays—and provided confirmatory evidence for an additional 7. Novel signals include: for IL-6, in the ABO gene (rs657152, p = 2.13×10−29); for ESR, at the HBB (rs4910472, p = 2.31×10−11) and UCN119B/SPPL3 (rs11829037, p = 8.91×10−10) loci; for MCP-1, near its receptor CCR2 (rs17141006, p = 7.53×10−13) and in CADM3 (rs3026968, p = 7.63×10−13); for hsCRP, within the CRP gene (rs3093077, p = 5.73×10−21), near DARC (rs3845624, p = 1.43×10−10), UNC119B/SPPL3 (rs11829037, p = 1.50×10−14), and ICOSLG/AIRE (rs113459440, p = 1.54×10−08) loci. Confirmatory evidence was found for IL-6 in the IL-6R gene (rs4129267); for ESR at CR1 (rs12567990) and TMEM57 (rs10903129); for MCP-1 at DARC (rs12075); and for hsCRP at CRP (rs1205), HNF1A (rs225918), and APOC-I (rs4420638). Our results improve the current knowledge of genetic variants underlying inflammation and provide novel clues for the understanding of the molecular mechanisms regulating this complex process