Biology subjects

Patmanidis, I.

Publications and source records attributed to Patmanidis, I..

5 recordsLinked to original sources

bioRxiv2026

Integrated genomics and transcriptomics reveal mechanisms of extreme dietary adaptation in vampire bats

Vampire bats are the only tetrapods that feed exclusively on blood. To uncover the molecular basis of this extreme dietary specialization, we generated six new reference genomes, including genomes of all three vampire bat species, and integrated comparative analyses of gene sequence evolution (selection signatures, duplications, and losses) with transcriptomic data from six major organs to identify shifts in gene expression. Our integrative analyses reveal sequence or expression changes in 150 genes that illuminate the genetic mechanisms underlying sanguivory. Through comparative analyses and experiments, we show that the enlarged vampire bat stomach has increased connective tissue content enabling extreme expansion, is pH-neutral, and exhibits reduced mucus production, together providing molecular insights into its shift from a digestive to an absorptive organ for water, electrolytes, and vitamins. We further uncover pathway-level molecular changes underlying altered gastrointestinal motility; trypsin-dependent protein digestion; upregulated amino acid catabolism with key aspects diverging from other mammals; impaired dietary fat digestion counterbalanced by increased fatty acid synthesis; defective sugar metabolism and natural insulin deficiency; enhanced heme iron absorption; and adult splenic erythropoiesis. Together, these findings reveal the molecular adaptations that enable one of the most extreme dietary transitions among vertebrates.

evolutionary biology↗

bioRxiv2026

Italia: A PARP-Directed Auger Electron-Emitting Agent for Targeted Radionuclide Therapy of Cancer

Poly(ADP-ribose) polymerase 1 (PARP1) is a central mediator of DNA damage repair and an established therapeutic target in homologous recombination-deficient cancers. Radiolabelled PARP inhibitors provide a strategy to deliver cytotoxic radiation directly to tumour DNA by exploiting PARP overexpression and trapping at sites of DNA damage. Here, we describe the design, radiosynthesis, and in vitro evaluation of [123I]Italia, a talazoparib-derived Auger electron-emitting agent for PARP-targeted radionuclide therapy. Stereochemically pure [123I]Italia, (8S,9R)-5-fluoro-8-(4-(iodo-123I)phenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one was synthesised in one step via copper-mediated iodo-deboronation, achieving activity yields >80% and molar activities >6.2 {+/-} 3.1 GBq/{micro}mol (n=8). UPLC analysis confirmed radiochemical purity >97%. Italia exhibited potent PARP1 inhibition (IC50 0.48 nM) and in silico predicted binding affinity comparable to talazoparib. In a panel of PARP-expressing cancer cell lines, [123I]Italia demonstrated highest uptake at 60 min, PARP-selective uptake, predominant nuclear localisation (up to 60% of added activity) and chromatin association consistent with PARP trapping (up to 15% of total activity recorded). Uptake was reduced more than 50-fold by addition of an excess of any PARP inhibitor (e.g. olaparib, talazoparib, and rucaparib) and in PARP1 knockout cells, confirming target specificity. Clonogenic assays showed a marked, added activity-dependent reduction in survival of PARP-expressing cells following a brief one-hour exposure, whereas PARP1-deficient cells were resistant. Collectively, these findings identify [123I]Italia as a promising PARP-targeted Auger electron-emitting theranostic candidate that warrants further in vivo evaluation.

cancer biology↗

bioRxiv2025

Directionality range in Emlen funnels

Emlen funnels can be used to study the birds ability to orient during the migratory seasons. Birds are so eager to migrate that they will jump in the direction in which they want to fly, even if they are placed in small cages during the night. Emlen funnels have therefore been used for decades to study the sensory capabilities and mechanisms that migratory birds use to find their way. A significant part of this research has focused on how night-migratory songbirds perceive the Earths magnetic field. Even though Emlen funnels have been proven quite successful in capturing the birds behavioural responses to different experimental conditions, the orientation behaviour of night-migratory songbirds in Emlen funnels is very noisy, i.e. tends to have a low signal to noise ratio. This noise makes Emlen funnel experiments very time consuming and limits the types of questions that can be studied to those which require very few different experimental conditions (permutations). Furthermore, the experimental design choices can be crucial, e.g. degree of blinding of the experimenters and data evaluators to the conditions tested, pre-testing of birds to make sure they are in a migratory state, and planning of the effective sample sizes. Hence, different traditions in experimental design choices can reduce reproducibility and comparability and render the interpretation of the results non-trivial. To better understand Emlen funnel data and the minimal requirements for good experimental design, we constructed and analyzed a large data set that we compiled by combining behavioural data from many previous Emlen funnel studies performed in Oldenburg. Our results provide realistic ranges for the expected orientation of the birds in Emlen funnels, which can be useful (and in some research crucial) for predicting the optimal sample sizes for future experiments. Our results thus offer concrete information for the design and analysis of statistically powerful future magnetic orientation experiments.

animal behavior and cognition↗

bioRxiv2024

Changes in flexibility but not in compactness underlie the thermal adaptation of prokaryotic adenylate kinases

Understanding the structural changes that enable enzymes to remain active in extreme thermal conditions is of broad scientific interest for both fundamental and applied biological research. Three key mechanisms that underlie the thermal adaptation of enzymes are modifications in structural flexibility, compactness, and the contacts formed among amino acids. However, most previous studies on these topics have been limited to small sample sizes or a narrow taxonomic focus, and the importance of these factors to thermal adaptation remains poorly understood. In this study, we combined molecular dynamics simulations and phylogenetic comparative analyses to thoroughly analyse the structural factors underlying thermal adaptation in adenylate kinase--a key enzyme involved in cellular energy balance and homeostasis--across 70 prokaryotic species. We detect systematic increases in the flexibility of the enzyme with temperature, both across and within species. In contrast, structural compactness appears to be almost completely independent of temperature. Finally, we uncover a remarkable diversity in the number and types of amino acid contacts observed in different adenylate kinases that cannot be explained solely by temperature. Our results suggest that there are multiple paths toward the adaptation of prokaryotic adenylate kinases to extreme thermal environments and that these paths are generally accessible through changes in flexibility. Lay summaryThe structure of a given enzyme can vary considerably among species, reflecting local environmental conditions to an extent. To this day, we do not have a clear picture of the impacts of the thermal environment on enzyme structure. To fill this gap, we performed a structural comparison of the enzyme adenylate kinase (ADK) from 70 species of bacteria and archaea. We find that rises in temperature tend to increase the flexibility of the enzyme. However, at any given temperature, ADKs from cold environments tend to be more flexible than those from hot environments. In contrast, the compactness of the enzyme did not vary consistently with temperature. Finally, we found that the pattern of amino acid contacts can vary dramatically across ADKs of different species, in a manner that cannot be predicted by temperature alone. Overall, our study shows that there are multiple ways to evolve an enzyme structure that can tolerate extreme temperatures, with a key constraint being maintaining sufficient flexibility at temperatures typically experienced by each species.

evolutionary biology↗

bioRxiv2020

Higher temperatures worsen the effects of mutations on protein stability

Understanding whether and how temperature increases alter the effects of mutations on protein stability is crucial for understanding the limits to thermal adaptation by organisms. Currently, it is generally assumed that the stability effects of mutations are independent of temperature. Yet, mutations should become increasingly destabilizing as temperature rises due to the increase in the energy of atoms. Here, by performing an extensive computational analysis on the essential enzyme adenylate kinase in prokaryotes, we show, for the first time, that mutations become more destabilizing with temperature both across and within species. Consistent with these findings, we find that substitution rates of prokaryotes decrease nonlinearly with temperature. Our results suggest that life on Earth likely originated in a moderately thermophilic and thermally fluctuating environment, and indicate that global warming should decrease the per-generation rate of molecular evolution of prokaryotes.

evolutionary biology↗