bluuebunny/crossref_metadata_2025 huggingface dataset:
Gas exchange, oxygen transport and metabolism in high-altitude waterfowl
Authors: Laguë Sabine L. , Ivy Catherine M. , York Julia M. , Dawson Neal J. , Chua Beverly A. , Alza Luis , Scott Graham R. , McCracken Kevin G. , Milsom William K.
Published: February 2025

High-altitude life poses physiological challenges to all animals due to decreased environmental oxygen (O
2
) availability (hypoxia) and cold. Supporting high metabolic rates and body temperatures with limited O
2
is challenging. Many birds, however, thrive at high altitudes. The O
2
-transport cascade describes the pathway involved in moving O
2
from the environment to the tissues encompassing: (i) ventilation, (ii) pulmonary O
2
diffusion, (iii) circulation, (iv) tissue O
2
diffusion, and (v) mitochondrial O
2
use for ATP production. Shared avian traits such as rigid lungs with cross-current gas exchange and unidirectional airflow aid in O
2
acquisition and transport in all birds. Many high-altitude birds, however, have evolved enhancements to some or all steps in the cascade. In this review, we summarize the current literature on gas exchange and O
2
transport in high-altitude birds, providing an overview of the O
2
-transport cascade that principally draws on the literature from high-altitude waterfowl, the most well-studied group of high-altitude birds. We close by discussing two important avenues for future research: distinguishing between the influences of plasticity and evolution and investigating whether the morphological and physiological differences discussed contribute to enhanced locomotor or thermogenic performance, a potential critical link to fitness.

This article is part of the theme issue ‘The biology of the avian respiratory system’.
Adaptation and conservation of CL-10/11 in avian lungs: implications for their role in pulmonary innate immune protection
Authors: Kunchala Srinivasa Reddy , van Dijk Albert , Veldhuizen Edwin J. A. , Haagsman Henk P. , Orgeig Sandra
Published: February 2025

The common avian origin of many zoonotic infections and epidemics warrants investigation into the mechanism of respiratory surface protection in reservoir species such as birds. Our recent molecular investigations on the evolution and pulmonary expression of an ancient family of proteins, the C-type lectins, have revealed unique molecular adaptations in the surfactant proteins avian SP-A1 (aSP-A1), aSP-A2 and aSP-C coupled with the loss of surfactant protein-D (SP-D) in the avian lineage. As surfactant proteins are members of the collectin family, a subgroup of the C-type lectins, an
in silico
search for related non-surfactant collectin proteins (Collectin-10 (CL-10) and Collectin-11 (CL-11)) in the NCBI genome database was conducted to understand their evolution in the avian lineage. In addition, both CL-10 and CL-11 gene expression in the lungs and other organs of zebra finches and turkeys was confirmed by PCR. These PCR-confirmed zebra finch and turkey CL-10 and CL-11 sequences were compared with sequenced and
in silico
-predicted vertebrate homologues to develop a phylogenetic tree. Compared with avian surfactant proteins, CL-10 and CL-11 are highly conserved among vertebrates, suggesting a critical role in development and innate immune protection. The conservation of CL-11 EPN and collagen domain motifs may compensate to some extent for the loss of SP-D in the avian lineage.

This article is part of the theme issue ‘The biology of the avian respiratory system’.
The influence of soft tissue volume on estimates of skeletal pneumaticity: implications for fossil archosaurs
Authors: Burton Maria Grace , Benito Juan , Mellor Kirsty , Smith Emily , Martin-Silverstone Elizabeth , O'Connor Patrick , Field Daniel J.
Published: February 2025

Air space proportion (ASP), the volume fraction in bone that is occupied by air, is frequently applied as a measure for quantifying the extent of skeletal pneumaticity in extant and fossil archosaurs. Nonetheless, ASP estimates rely on a key assumption: that the soft tissue mass within pneumatic bones is negligible, an assumption that has rarely been explicitly acknowledged or tested. Here, we provide the first comparisons between estimated air space proportion (where the internal cavity of a pneumatic bone is assumed to be completely air-filled) and true air space proportion (ASPt, where soft tissues present within the internal cavities of fresh specimens are considered). Using birds as model archosaurs exhibiting postcranial skeletal pneumaticity, we find that estimates of ASPt are significantly lower than estimates of ASP, raising an important consideration that should be acknowledged in investigations of the evolution of skeletal pneumaticity and bulk skeletal density in extinct archosaurs, as well as in volume-based estimates of archosaur body mass. We advocate for the difference between ASP and ASPt to be explicitly acknowledged in studies seeking to quantify the extent of skeletal pneumaticity in extinct archosaurs, to avoid the risk of systematically overestimating the volume fraction of pneumatic bones composed of air.

This article is part of the theme issue ‘The biology of the avian respiratory system’.
A synchrotron X-ray CT-based 3D atlas of the songbird syrinx with single muscle fibre resolution implies fine motor control of syringeal vocal folds
Authors: Adam Iris , Zai Anja T. , Stepien Anna E. , Yamahachi Homare , Schlepütz Christian M. , Hahnloser Richard H. R. , Elemans Coen P. H.
Published: February 2025

Avian vocalizations are produced by precisely coordinated motion of the respiratory, syringeal and upper vocal tract systems. Syringeal muscles are controlled with unprecedented resolution, down to independent control of individual muscle fibres. However, we currently lack an anatomical description of syrinx muscles at single fibre resolution. Here, we combined a micron-resolution synchrotron X-ray CT scan of the zebra finch syrinx with micro-dissections of independent specimens to resolve syrinx muscle morphology at individual muscle fibre level. We define two new, previously unknown muscles and update the fibre trajectories and attachment sites of three previously described muscles. Our new insights into the fine anatomy of syrinx muscles show that not one, but both avian vocal folds can be directly controlled by contracting syrinx muscles. Thus, our data reveal novel anatomical complexity with consequences for the biomechanics and motor control of sound production.

This article is part of the theme issue 'The biology of the avian respiratory system'.
Respiratory contributions to birdsong—evolutionary considerations and open questions
Authors: Goller Franz
Published: February 2025

Respiration plays a central role in avian vocal behaviour by providing the airstream that induces vibration of vocal folds. In this role, respiratory movements dictate the coarse temporal pattern of song, while simultaneously fulfilling its vital functions. Whereas these aspects have been investigated in oscines, little information exists in other taxa. Broad taxonomic information is, however, necessary for addressing questions regarding evolutionary specializations of the respiratory system. Acoustic recordings of unstudied taxa suggest that rapid action by respiratory muscles is a basal trait within birds. In addition to controlling the timing of vocalization, respiratory activity also influences acoustic features such as sound amplitude and frequency. The latter is more strongly influenced by respiratory driving pressure in non-vocal learners. Singing, as a highly dynamic respiratory activity presents an opportunity for studying detailed ventilation patterns and thus could give insight into the basic control of airflow in the avian lung–air sac system. Although we have learned many details of how respiratory control is tied into cortical song control, many open questions remain. Control of respiratory pacemaker circuitry by upstream vocal control centres, respiratory input in initiation of vocalization and the use of online feedback from the respiratory system are all incompletely understood.

This article is part of the theme issue ‘The biology of the avian respiratory system’.
Structure and function of the avian respiratory system
Authors: Maina J. N.
Published: February 2025

Among the extant air-breathing vertebrates, the avian respiratory system is the most efficient gas exchanger. Novel morphological and physiological adaptations and specializations largely explain its exceptional functional superiority. Anatomically, the avian respiratory system is separated into lungs that serve as gas exchangers and air sacs that operate as ventilators. Utterly rigid, the avian lungs are deeply fixed to the ribs and the vertebrae. A thin blood–gas barrier (BGB), vast respiratory surface area and large pulmonary capillary blood volume generate high total pulmonary morphometric diffusing capacity of O
2
. The weak allometric scaling of the thickness of the BGB indicates optimization for gas exchange; the negative scaling and strong correlation between the surface density of the respiratory surface area and body mass show the extreme subdivision of the gas exchange tissue; and the respiratory surface area, the pulmonary capillary blood volume and the total pulmonary morphometric diffusing capacity of O
2
correlate strongly and positively with body mass. The arrangement of the structural components of the exchange tissue form crosscurrent-, countercurrent-like- and multicapillary serial arterialization gas exchange designs. By synchronized actions of the air sacs, the palaeopulmonic part of the of the avian lung is efficiently ventilated continuously and unidirectionally in a caudocranial direction.

This article is part of the theme issue ‘The biology of the avian respiratory system’.
Development of postcranial pneumaticity in the turkey (
Meleagris gallopavo
): insight from the forelimb skeleton
Authors: Gutherz Samuel Benjamin , Stover Kristin , Sze Nicholas , Groenke Joseph R. , O'Connor Patrick M.
Published: February 2025

Postcranial skeletal pneumaticity is a phenomenon in birds in which epithelial extensions of the lung–air sac system aerate bones. Detailed development of this phenotype remains largely unknown. Here, we investigate changes in bone, soft tissue and air space volume in the developing humerus of turkeys using computed tomography and micro-computed tomography. Employing a two-phase approach, we first tracked humeral air space development
in vivo
in domesticated turkeys between week 10 (W10) and W18 post-hatch. In phase 2, we analysed air space and marrow volume change through the first 22 weeks of post-hatch development. Our results indicate that pneumatization of the humerus begins between W2 and W4 post-hatch, with air spaces expanding distally from the proximal humerus. Internal air space expands most rapidly between W7 and W9, with maximal volume reached at W15. Increased marrow growth occurs between W13 and W19, coincident with stabilization and a potential decline in relative air space volume. Our study highlights a dynamic relationship between bone, marrow and pneumatic epithelium, suggesting pneumaticity expression is likely impacted by both within-bone tissue growth dynamics and extrinsic factors related to forelimb function. This work provides the necessary gross anatomical framework for subsequent analyses of tissue-level and cellular mechanisms related to the pneumatization process.This article is part of the theme issue ‘The biology of the avian respiratory system’.
Genotypic and phenotypic analyses of two distinct sets of Pseudomonas aeruginosa urinary tract isolates
Authors: Ebrahim H. , Haldenby S. , Moore M.P. , Dashti A.A. , Floyd R.V. , Fothergill J.L.
Published: February 2025

Introduction. Urinary tract infections (UTIs) are associated with a high burden of morbidity, mortality and cost. Pseudomonas aeruginosa employs a myriad of virulence factors, including biofilm formation and motility mechanisms, to cause infections including persistent UTIs. P. aeruginosa is highly resistant to antibiotics, and the World Health Organization has identified it as a pathogen for which novel antimicrobials are urgently required.

Gap statement. Genotypic and phenotypic characterization of P. aeruginosa from UTIs is underreported. In addition, the rise of antimicrobial resistance (AMR) is a cause for concern, particularly in many countries where surveillance is severely lacking.

Aim. To identify genotypic and phenotypic characteristics of P. aeruginosa UTI isolates sourced from the UK and the state of Kuwait, with an emphasis on genotypic diversity and AMR.

Methods. Twenty-three P. aeruginosa UTI isolates were sourced from the UK and Kuwait. To establish the phenotypes of UK isolates, growth analysis, biofilm formation assays, motility assays and antibiotic disc diffusion assays were performed. Whole-genome sequencing, antimicrobial susceptibility assays and in silico detection of AMR-associated genes were conducted on both sets of isolates.

Results. In terms of their phenotypic characteristics and genomic composition, the UTI isolates varied. Multiple resistance genes are associated with resistance to various classes of antibiotics, such as aminoglycosides, fluoroquinolones and β-lactams, particularly in isolates from Kuwait. Extreme antibiotic resistance was detected in the isolates obtained from Kuwait, indicating that the country may be an antibiotic resistance hotspot.

Conclusion. This study highlights that isolates from UTIs are diverse and can display extremely high resistance. Surveillance in countries such as Kuwait is currently limited, and this study suggests the need for greater surveillance.
100+ years of phase variation: the premier bacterial bet-hedging phenomenon
Authors: Bayliss Christopher D. , Clark Jack L. , van der Woude Marjan W.
Published: February 2025

Stochastic, reversible switches in the expression of Salmonella flagella variants were first described by Andrewes in 1922. Termed phase variation (PV), subsequent research found that this phenomenon was widespread among bacterial species and controlled expression of major determinants of bacterial–host interactions. Underlying mechanisms were not discovered until the 1970s/1980s but were found to encompass intrinsic aspects of DNA processes (i.e. DNA slippage and recombination) and DNA modifications (i.e. DNA methylation). Despite this long history, discoveries are ongoing with expansions of the phase-variable repertoire into new organisms and novel insights into the functions of known loci and switching mechanisms. Some of these discoveries are somewhat controversial as the term ‘PV’ is being applied without addressing key aspects of the phenomenon such as whether mutations or epigenetic changes are reversible and generated prior to selection. Another ‘missing’ aspect of PV research is the impact of these adaptive switches in real-world situations. This review provides a perspective on the historical timeline of the discovery of PV, the current state-of-the-art, controversial aspects of classifying phase-variable loci and possible ‘missing’ real-world effects of this phenomenon.
Colonic inflammation modulates the intestinal circadian landscape
Authors: Butler Thomas D , Downton Polly , Dickson Suzanna H , Luengas-Martinez Andrea , Simpkins Devin A , Khoo Isabel , Veal Sarah , West Alexander C , Adamson Antony D , Bechtold David A , McLaughlin John T , Gibbs Julie E
Published: February 2025

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that carries significant morbidity. The circadian (24h) clock regulates many aspects of immunity and circadian disruption is implicated in inflammatory disease. We examined the impact of acute dextran sulphate sodium-induced colitis on the intestinal circadian landscape and investigated consequences of intestinal epithelial cell (IEC) clock disruption on immune function in health and under inflammatory stress. Within the inflamed colon, we observed attenuated IEC clock function. Furthermore,de novooscillations in numbers of colonic regulatory T cells emerged, associated with diurnal variation in proliferation and activation markers. IEC-specific deletion of core clock geneBmal1drove alterations in the rhythmic colonic transcriptome (impacting key immune pathways) and marked damping of microbiota rhythmicity. IEC-specificBmal1deletion did not impact colitis severity. These results highlight the impact of colonic inflammation on circadian processes and suggest that circadian logic could be applied in IBD treatment.
Quantitative systems pharmacology modeling of pyrrolobenzodiazepine antibody-drug conjugates targeting BCMA
Authors: Lam Inez , Dai David , Arends Rosalinda H. , Reddy Venkatesh Pilla , Ball Kathryn , Gabhann Feilim Mac
Published: February 2025

Antibody-drug conjugates (ADCs) are novel therapeutics combining two molecules linked together: an antibody that provides targeting to specific cells, and a cytotoxic drug (warhead) that can deconjugate from the antibody and kill those cells. The warhead by itself would be too nonspecific and toxic; the antibody by itself would be insufficiently effective at killing the cells. As more and more ADCs enter the drug development pipeline, understanding the mechanistic reasons behind efficacy and toxicity is critical to evaluating both successful and failed trials. Here, we have developed a mechanistic computational model of ADCs, and specifically parameterize it using data for MEDI2228, an anti-BCMA antibody conjugated to pyrrolobenzodiazepine (PBD) warheads. We build the model to track not only the concentrations of ADC and its released warhead drug inside and outside the cell, but also to track the recent history of the warhead, so that we can distinguish between pathways for on-target and bystander (nontargeted) cell killing. We show that this effect is predicted to be small underin vitroconditions due to dilution in large volumes of media, but likely to form a significant part of both targeted and nontargeted cell killingin vivo, where the extracellular volume has less of a dilution effect. We also explore the impact of key design parameters of ADCs, including drug to antibody ratio (DAR), warhead potency, and lipophilicity; this analysis demonstrates the balance needed between killing of targeted and nontargeted cells. Using this quantitative systems pharmacology model, we can generate insights for optimization of ADC design and determine which factors are most critical to efficacy and toxicity, leading to more informed and rational development of cancer therapies.
Differential Avian Responses to Coffee Farming Lead to Community Homogenization in a Working Landscape in Jardín, Colombia
Authors: Cediel Fernando , Ruíz-Gutiérrez Viviana , Echeverri Alejandra , Parra Juan. Luis
Published: February 2025

In Colombia, coffee production has an ingrained cultural and economic importance. Coffee is cultivated in biodiverse areas using a variety of practices ranging from sun-exposed monocultures to mixed and shaded plantations. Management practices on this working landscape alter the composition of bird communities. We hypothesize that coffee agroecosystems homogenize bird communities by favoring the occupancy of non-forest dependent bird species and deterring forest dependent birds. We evaluate the effects of coffee plantations and associated metrics of vegetation structure on a subset of bird species in an agroforestry landscape in the Western Andes in Colombia and evaluate the hypothesis of community homogenization. We collected data in two consecutive years in 153 sites in coffee plantations and other habitats in Jardín, Colombia. In order to evaluate birds’ response to changes in the working landscape we made single-season occupancy models and used five covariates: coffee (binary covariate), foliage height diversity (FHD) and canopy height (CH) as proxies for coffee management practices, human footprint (LHFI), and elevation. Finally, we used generalized dissimilarity models (GDM) with the same covariates and geographical distance to evaluate the homogenization hypothesis among coffee sites. We identified 193 species (six endangered and five endemics) and modeled occupancy of 74 species. Coffee plantations significantly decreased the occupancy of 14 species while 13 were favored. In general, non-forest dependent species preferred lower FHD and lower CH values, and occurred at lower elevations with high LHFI. On the contrary, forest dependent species preferred higher FHD and CH, and were found at higher elevations. The GDM with best fit supported the hypothesis that coffee sites tend to be more similar than no-coffee sites, and that elevation and FHD explained most of the variation in dissimilarity. The working landscape in Jardín holds an important community of birds but coffee plantations are driving its homogenization. We anticipate that non-forest dependent birds will continue to colonize working landscapes, unless structural vegetation changes are promoted. Increasing FHD and CH is a potential strategy to improve forest dependent bird occupancy and reduce homogenization in Jardín.
Distal mutations enhance catalysis in designed enzymes by facilitating substrate binding and product release
Authors: Zarifi Niayesh , Asthana Pooja , Doustmohammadi Hiva , Klaus Cindy , Sanchez Janet , Hunt Serena E , Rakotoharisoa Rojo V , Osuna Sílvia , Fraser James S , Chica Roberto A
Published: February 2025

The role of amino-acid residues distant from an enzyme's active site in facilitating the complete catalytic cycle—including substrate binding, chemical transformation, and product release—remains poorly understood. Here, we investigate how distal mutations promote the catalytic cycle by engineering mutants of three de novo Kemp eliminases containing either active-site or distal mutations identified through directed evolution. Kinetic analyses, X-ray crystallography, and molecular dynamics simulations reveal that while active-site mutations create preorganized catalytic sites for efficient chemical transformation, distal mutations enhance catalysis by facilitating substrate binding and product release through tuning structural dynamics to widen the active-site entrance and reorganize surface loops. These distinct contributions work synergistically to improve overall activity, demonstrating that a well-organized active site, though necessary, is not sufficient for optimal catalysis. Our findings reveal critical roles that distal residues play in shaping the catalytic cycle to enhance efficiency, yielding valuable insights for enzyme design.
Functional, Immunogenetic, and Structural Convergence in Influenza Immunity between Humans and Macaques
Authors: Sangesland Maya , Li Ning , Tsybovsky Yaroslav , Rodgers Magan D , Han Julianna , Rodriguez Alesandra J , Ferguson James A , Henry Amy R , Smith Sarah C , Roberts-Torres Jesmine , Gillespie Rebecca A , Liu Cuiping , Merriam Jonah , Stephens Tyler , Williams Connor , Maestle Emma , Corcoran Martin , Ravichandran Michelle , Creanga Adrian , Andrews Sarah F , Pierson Theodore C , Karlsson Hedestam Gunilla B , Schramm Chaim A , Reed Douglas S , Douek Daniel C , Zhou Tongqing , Ward Andrew B , Kanekiyo Masaru
Published: February 2025

Human B cell immunity to the influenza hemagglutinin (HA) stem region, a universal influenza vaccine target, is often stereotyped and immunogenetically restricted, posing challenges for study outside humans. Here, we show that macaques vaccinated with a HA stem immunogen elicit human-like public B cell lineages targeting two major conserved sites of vulnerability, the central stem and anchor epitopes. Central stem antibodies were predominantly derived from VH1-138, the macaque homolog of human VH1-69, a VH-gene preferentially used in human central stem broadly neutralizing antibodies (bnAbs). Similarly, macaques produced anchor bnAbs with the human-like NWP motif. Both bnAb lineages were functionally and structurally analogous to their human counterparts, with recognition mediated largely by germline-encoded motifs. Thus the macaque immunoglobulin repertoire supports human-like public bnAb responses to influenza HA. Moreover, this underscores the utility of homologous germline-encoded immunity, suggesting that immune repertoires of macaques and humans may have been similarly shaped during evolution.
Changes in the health-related ecosystem services and disservices provided by urban trees over multiple decades in a small city
Authors: Kwong Russell , Victor Thomas E. , Dijstelbloem Noa , Dong Zhou Y. , Robillard Ava M. , Gagnon Willa A. , Simon Christina S. , Radhakrishnan Camille I. , Peralta Keily A. , Youngstrom Elan C. , Terjesen Emma C. , Tsignadze Maia , Okuyama Daphne , Ma Moheng , Katz Daniel S.W.
Published: February 2025

The effects of urban trees on public health should change over decades due to shifts in tree composition and abundance, environmental conditions, human demography, and disease incidence. However, there are few case studies documenting changes in the health-related ecosystem services and disservices provided by trees over time. Here we use seven tree censuses to quantify changes in the effects of city-owned trees on air pollution, allergenic pollen, hydrology, and heat due to shifts in tree abundance and environmental conditions in Ithaca, New York, a small city in the Northeastern United States. We also review how shifts in disease incidence have affected these trees’ health consequences. From 2005 to 2021, trees removed 20% more ozone and 268% more PM2.5; they also removed substantially more runoff and had higher cooling capacity. In contrast, the amount of certain air pollutants removed by trees dropped from 2005 to 2021 for sulfur dioxide (361 kg/yr to 8 kg/yr), carbon monoxide (65 kg/yr to 32 kg/yr), and nitrogen dioxide (380 kg/yr to 298 kg/yr) as their ambient concentrations dropped. Pollen production by street trees from 1947 to 2021 initially dropped due to Dutch elm disease but has quadrupled since the 1980s due to increases in several high-pollen producing genera. Overall, this study illustrates how the public health effects of trees vary over decades due to changes in tree composition and abundance, environmental conditions, and changes in disease incidence and human demography, emphasizing the importance of incorporating long-term perspectives into contemporary tree management decisions.

Highlights

● Urban trees health-related ecosystem services changed over decades in a case study

● The removal of SO2, NO2, and CO by urban trees is diminishing due to cleaner air

● Shifts in tree composition have had large effects on allergenic pollen production

● Changes in human disease incidence over decades mediate trees health effects
STAT3 Sustains Tumorigenicity Following Mutant KRAS Ablation
Authors: D’Amico Stephen , Kirillov Varvara , Liu Jingxuan , Qiu Zhijuan , Lei Xinyuan , Qin Hong , Sheridan Brian S. , Reich Nancy C.
Published: February 2025

Oncogenic KRAS mutations underlie some of the deadliest human cancers. Genetic or pharmacological inactivation of mutant KRAS is not sufficient for long-term control of advanced tumors. Using a conceptual framework of pancreatic ductal adenocarcinoma, we find that CRISPR-mediated ablation of mutant KRAS can terminate tumor progression contingent on the concomitant inactivation of STAT3. STAT3 inactivation is needed to ensure that KRAS-ablated tumor cells lose their malignant identity. Mechanistically, the combined loss of mutant KRAS and STAT3 disrupts a core transcriptional program of cancer cells critical to oncogenic competence. This in turn impairs tumor growth in mice and enhances immune rejection, leading to tumor clearance. We propose that the STAT3 transcriptional program operating in cancer cells enforces their malignant identity, rather than providing classical features of transformation, and shapes cancer persistence following KRAS inactivation. Our findings establish STAT3 as a critical enforcer of oncogenic identity in KRAS-ablated tumors, revealing a key vulnerability that could be exploited for combination therapies.

Significance

The limited clinical success of KRAS inhibitors points to the need to identify means by which tumor cells maintain stemness and immune evasion. We make an unprecedented finding that the STAT3 transcription factor can sustain tumorigenicity of pancreatic cancer cells following depletion of the KRAS oncogenic driver. The results have important implications for successful therapeutic intervention.
Improving allometric models to estimate the proboscis length of tropical bees
Authors: Frühholz Kilian , Kuba Kenneth , Pitz Maximilian , Windl Julia , Keller Alexander , Brehm Gunnar , Rasmussen Claus , Leonhardt Sara Diana , Mendes Diniz Ugo
Published: February 2025

The proboscis length of bees is a key morphological trait shaping communities, pollination networks, and likely their responses to habitat loss. Despite its importance, it is rarely considered in ecological studies because of logistic limitations in obtaining accurate measurements across many different species. In two previous studies, the proboscis length of temperate bee species was estimated based on body size and bee family. However, bee taxa partially occurring in the tropics might deviate from this allometric relationship due to different functional constraints. Thus, we tested if equations developed for temperate bees can accurately predict the proboscis length in Meliponini, Euglossini (both Apidae), and Augochlorini (Halictidae), three ubiquitous and highly important tribes of tropical bees. We measured the intertegular distance (as a proxy of body size measurement) and the proboscis length of 892 specimens of 105 tropical species. We used these measurements to evaluate the previous model and found that its estimations lacked accuracy when applied to tropical bees, particularly to Meliponini and Euglossini. We developed new allometric equations estimating the proboscis length based on the intertegular distance, using (sub-) genera as an additional predictive variable to refine the estimations. We tested our approach by creating a test model for Meliponini, trained with only 80 % of the data, and evaluated this model using the remaining 20 %, resulting in a high accuracy of estimates. Our results shed additional light on the nature of the proboscis length-body size allometric relationship in tropical bees and provide a tool for future studies on the functional ecology of bees and their interactions with plants.
Using time-series remote sensing to identify and track individual bird nests at large scales
Authors: Ernest SK Morgan , Garner Lindsey , Weinstein Ben , Frederick Peter , Senyondo Henry , Yenni Glenda Marie , White Ethan P
Published: February 2025

The challenges of monitoring wildlife often limits the scales and intensity of the data that can be collected. New technologies - such as remote sensing using unoccupied aircraft systems (UAS) - can collect information more quickly, over larger areas, and more frequently than is feasible using ground-based methods. While airborne imaging is increasingly used to produce data on the location and counts of individuals, its ability to produce individual-based demographic information is less explored. Repeat airborne imagery to generate an imagery time-series provides the potential to track individuals over time to collect information beyond one-off counts, but doing so necessitates automated approaches to handle the resulting high-frequency large-spatial scale imagery. We develop an automated time-series remote sensing approach to identifying wading bird nests in the Everglades ecosystem of Florida, USA to explore the feasibility and challenges of conducting time-series based remote sensing on mobile animals at large spatial scales. We combine a computer vision model for detecting birds in weekly UAS imagery of colonies with biology-informed algorithmic rules to generate an automated approach that identifies likely nests. Comparing the performance of these automated approaches to human assessment of the same imagery shows that our primary approach identifies nests with comparable performance to human photo assessment, and that a secondary approach designed to find quick-fail nests resulted in high false positive rates. We also assessed the ability of both human photo assessment and our primary algorithm to find ground-verified nests in UAS imagery and again found comparable performance, with the exception of nests that fail quickly. Our results show that automating nest detection, a key first step towards estimating nest success, is possible in complex environments like the Everglades and we discuss a number of challenges and possible uses for these types of approaches.
Identification of astrocytomas through serum protein fingerprint using MALDI-TOF MS and machine learning
Authors: Lazari Lucas Cardoso , Silva Janaina M , Donado Priscila R. S. , Shinjo Sueli M. O. , Fernandes Livia R , Ieva Antonio Di , Marie Suely K. N. , Palmisano Giuseppe
Published: February 2025

Gliomas account for most brain malignancies, with astrocytomas being the most common subtype. Among these, glioblastoma (GBM) stands out as the most aggressive form, exhibiting a median survival time of just 15 months despite intensive therapy. Current diagnostic practices rely on magnetic resonance imaging (MRI) and histopathological analysis, which often necessitate invasive surgical sampling. This underscores the need for minimally invasive diagnostic tools capable of characterizing glioma progression and guiding treatment strategies. Advances in glioma classification have integrated histological and molecular markers, notably IDH1 mutations, which are prognostically significant, particularly in low-grade gliomas and in the previously defined secondary GBM (IDH-mutant astrocytoma grade 4). This study aimed to explore the potential of serum proteomics as a non-invasive diagnostic tool using MALDI-TOF mass spectrometry (MS) combined with machine learning techniques. We analyzed serum samples from 269 patients, employing machine learning models to differentiate between healthy individuals and astrocytoma patients. The MALDI-TOF MS approach achieved a balanced accuracy of 94.5% in distinguishing GBM patients from healthy controls. However, it showed limited efficacy in classifying tumor grades or determining IDH1 mutational status. Further investigation using bottom-up proteomics by GeLC-MS/MS identified potential biomarkers, such as transthyretin, previously associated with high-grade gliomas. These findings highlight the promise of MALDI-TOF MS in identifying serum-based biomarkers for astrocytoma diagnosis. While the results are promising, further validation in independent cohorts is essential to assess the clinical utility of these biomarkers for non-invasive glioma diagnostics and patient monitoring.
Photoaffinity ligand of Cystic Fibrosis corrector VX-445 identifies SCCPDH as an off-target
Authors: Kim Minsoo , Kim Kwangho , Lee Jesun , Barny Lea A , Skaggs LaToya , Romaine Ian , Jeon KyuOk , Codreanu Simona G , Sherrod Stacy D , McLean John A , Naren Anjaparavanda , Sulikowski Gary A , Plate Lars
Published: February 2025

Cystic fibrosis (CF) pharmacological correctors improve Cystic Fibrosis transmembrane conductance regulator (CFTR) protein trafficking and function. Several side-effects from these correctors and adverse drug interactions have been reported, emphasizing the need to understand off-targets. We synthesized VU439, a functionalized photoaffinity ligand (PAL) of VX-445. Chemoproteomics analysis by mass spectrometry (MS) was used to identify crosslinked proteins in CF bronchial epithelial cells expressing F508del CFTR. We identified saccharopine dehydrogenase-like oxidoreductase (SCCPDH), an uncharacterized putative oxidoreductase, as a VX-445 specific off-target. We then characterized changes in the metabolomic profiles of cells overexpressing SCCPDH to determine the consequence of VX-445 binding to SCCPDH. These data show dysregulation of amino acid metabolism and a potential inhibitory activity of VX-445 on SCCPDH. The identified off-target may explain exacerbation of psychological symptoms observed in the clinic, thus emphasizing the need for further optimization of correctors.
A network-based comparative method to study reptile scalation and other homologous two-dimensional patterns
Authors: Krone Isaac W
Published: February 2025

From the heads of sunflowers to insect wings to the scales on the heads of reptiles, discrete, two-dimensional patterns abound in the natural world. While some of these patterns, like plant phyllotaxis and the regular scalation of snake bodies, are created by repetition following a simple algorithm, others are far more complex and idiosyncratic, containing irregular elements that nonetheless have clear homology relationships between species. The recurrence of these complex but homologous patterns (not to mention the basic logic of ontogeny) indicate that they must be mechanistically patterned, and therefore be comparable with each other, yet researchers have not developed holistic methods for comparing them. Here, I present such a method, developed to systematically compare reptile scalation patterns (often referred to as "pholidosis,") but applicable in general to surface patterns constructed from units with clear homology relationships. Rather than treating scale numbers and scale adjacency relationships as discrete characters, I draw inspiration from the techniques of geometric morphometrics and anatomical network analysis to analyze the pattern of pholidosis as a network spread across the body of the animal. I describe a simple method for producing these networks and then describe and implement an algorithm that provides an edit-distance measure between networks, allowing for comparative analysis of their topologies-a "topometric" tool. Using a group of fossorial lizards (family Dibamidae) as a study system, I demonstrate the utility of these techniques in understanding the evolution of scalation patterns in a comparative context, investigating the relationships between pholidosis patterns, phylogeny, morphology, ecology and biogeography in this poorly-understood clade. These techniques are implemented in an R package, "pholidosis."
Advancing Heterospecific Sterile Insect Technique AgainstDrosophila suzukii:selection of the optimal irradiation dose forD. melanogastermales
Authors: Cerasti Flavia , Mastrantonio Valentina , Cemmi Alessia , Di Sarcina Ilaria , Cristofaro Massimo , Porretta Daniele
Published: February 2025

The spotted-wing drosophila (Drosophila suzukii), a highly invasive agricultural pest, poses significant challenges to fruit production worldwide. Traditional chemical control methods are costly and raise concerns about resistance and environmental sustainability. The Heterospecific Sterile Insect Technique (h-SIT) has emerged as a promising alternative, using sterile heterospecific males (Drosophila melanogaster) to suppressD. suzukiipopulations through reproductive interference. However, optimizing irradiation doses is critical to balancing male sterility, maintaining biological quality and mating performances. This study aimed to determine the optimal irradiation dose forD. melanogastermales by assessing their sterility, longevity, and courtship behavior following exposure to gamma-ray doses ranging from 80 to 180 Gy. Results showed a significant reduction in fertility across all irradiation doses, with near-complete sterility at 180 Gy. However, longevity decreased with increasing doses, with males irradiated at 160–180 Gy showing a lifespan reduction of up to 50 days compared to controls. Behavioral trials revealed that irradiatedD. melanogastermales retained their courtship ability towardD. suzukiifemales, although males exposed to 160 Gy exhibited reduced courtship activity. These findings highlight that, among the tested doses, 80 Gy emerged as the most effective, preserving male longevity and mating performance while significantly reducing fertility. While 180 Gy achieved the highest sterility, the potential lifespan and courtship behavior trade-offs warrant further evaluation. Future studies should evaluate field performance to refine the balance between sterility, longevity, and mating performances for effectiveD. suzukiipopulation suppression.
Identification ofde novovariants from parent-proband duos via long-read sequencing
Authors: Boukas Leandros , Délot Emmanuèle C. , Pitsava Georgia , Lambert Christine , Fanslow Cairbre , Baybayan Primo , Belhadj Sami , Losic Bojan , Harting John , Bluske Krista , LoTempio Jonathan , Al-Kouatly Huda , Karam Rachid , Rowell William , Xiao Changrui , Vilain Eric , Berger Seth I.
Published: February 2025

Whilede novovariants cause many Mendelian disorders, their detection currently requires sequencing of the proband and both biological parents. This is not feasible when only one parent is available, a limitation for millions of families. We developedduoNovo, which identifiesde novovariants from single parent-proband duos using long-read sequencing followed by haplotype reconstruction and detection of identical-by-descent haplotype blocks. We sequenced 40 trios and appliedduoNovoto each of the 80 duos constructed by masking one parent, classifying over 20 million variants. We evaluatedduoNovo’s performance against classifications obtained using the full trios (which included over 1,900de novovariants), demonstrating very high precision and low error rate, and perfect accuracy among variants absent from gnomAD.duoNovois freely available to the community as an R package, and may represent an example where long-read sequencing provides clear diagnostic benefit over short-read sequencing.
Epidemic-Ready Primary Health Care and the Application of the 717 Metrics: A Case Study on a Measles Outbreak in Sierra Leone, January-March 2024
Authors: Eleeza Oliver , Barrera-Cancedda Amy Elizabeth , Mutebi Ronald R. , Njenga Amon , Vandi Mohamed A. , Mearns Stacey , Yakubu AbdulRaheem , Toure Mame , Michaels-Strasser Susan
Published: February 2025

The COVID-19 pandemic exposed vulnerabilities in health systems’ abilities to detect, report, and respond to threats. Inadequate preparedness led to healthcare worker infections (HCW), essential service disruptions, and impacts on communities. Primary health care (PHC) is often overlooked in health security initiatives. Epidemic Ready Primary Health Care (ERPHC) is an initiative that strengthens PHC facilities to prevent, detect and respond to outbreaks, while maintaining essential services.

ICAP at Columbia University, the Ministry of Health of Sierra Leone, and Resolve to Save Lives is implementing a multi-year ERPHC project in Sierra Leone. A retrospective data review of 52 confirmed measles cases across four PHC facilities from January – March 2024 was conducted. Data is presented using an adapted 7-1-7 quality improvement approach for detection and notification to evaluate the key tenants of ERPHC: speed, safety, surge.

Out of 52 confirmed cases, 98% and 100% met the first “7” and “1” for detection and notification. Immediate case management and safety actions were completed for all 52 cases (100%). Zero facilities were able to implement two readiness parameters for surge: sufficient supplies and referral pathways. Key bottlenecks included late presentation to health facilities, delayed notification via the electronic case-based surveillance system, inadequate PPE, and no updated referral pathways.

These results underscore the need to scale and implement ERPHC, using adapted 7-1-7 metrics, in PHC facilities. HCW safety, increased community engagement, national supply chain mechanism strengthening, and established patient referral pathways need to be the foci of further health security investment in Sierra Leone.
Single-cell atlas of BAL from preschool cystic fibrosis reveals key inflammatory pathways modified by the CFTR modulator ivacaftor in the early life lung
Authors: Maksimovic Jovana , Shanthikumar Shivanthan , Howitt George , Dixit Gunjan , Hickey Peter F , Anttila Casey , Brown Daniel V. , Senabouth Anne , Amann-Zalcenstein Daniela , Powell Joseph E. , Ranganathan Sarath C. , Oshlack Alicia , Neeland Melanie R.
Published: February 2025

Aberrant inflammation and structural lung damage occurs early in life for people with cystic fibrosis (CF). Even in the era of CFTR modulators, anti-inflammatory therapy may still be needed to prevent establishment and lifelong consequences of bronchiectasis. In this study, we integrated transcriptome-wide single-cell RNA sequencing data, highly multiplexed surface protein expression, and functional pathway analysis to create a comprehensive paediatric lower airway atlas of 44 immune and epithelial cell populations in bronchoalveolar lavage (BAL). We then analysed this atlas to investigate inflammatory cell responses in children with CF to show widespread dysregulation of macrophage function in the preschool CF lung. This included alterations in pathways associated with SARS-COV and influenza responses, TNF/IFN signalling, cholesterol homeostasis, and pulmonary fibrosis that were further altered by the early development of bronchiectasis. We showed that the CFTR modulator ivacaftor restores some of these macrophage-related functional deficits and reduces expression of pathways associated with neutrophil infiltration, however the modulator lumacaftor/ivacaftor was not associated with any detectable change in transcriptional response. This work represents a comprehensive, multi-omic single-cell analysis of bronchoalveolar lavage from preschool children and the results inform the future development of anti-inflammatory therapy for children with CF.
Machine Learning-Based Drug Response Prediction Identifies Novel Therapeutic Candidates for Colorectal Cancer Cell Line KM-12
Authors: Chanchabi Cyrine , Paul Conception , Coulon Vincent , Cicalini Ilaria , Pierogostino Damiana , Vishwakarma Sachin , Hernández-Hernández Saiveth , Ballester Pedro J. , Hahne Michael
Published: February 2025

One major hurdle in the discovery of new drugs is the limited capacity of traditional screening methods to efficiently explore the immense space of drug candidates. To bypass this difficulty, computational approaches such as virtual screening (VS) have been developed supported by Machine Learning (ML) models to predict the activities of drug-like molecules on a given target. We developed a ML model for VS of a library of 25 million highly-diverse synthesis-on-demand molecules against the KM-12 colorectal cancer (CRC) cell line. By combining different biological readouts, we discovered compounds with a novel chemical scaffold, not yet described in the context of CRC, with either a prominent cytotoxic or cytostatic effect. This finding underpins the strength of our ML-guided VS protocol in discovering promising CRC drug leads triggering altered biological responses.