bluuebunny/crossref_metadata_2025 huggingface dataset:
Phytochemical drivers of insect herbivory: a functional toolbox to support agroecological diversification
Authors: Grosjean Jeremy , Pashalidou Foteini G. , Fauvet Aude , Baillet Aurore , Kergunteuil Alan
Published: July 2024

Plant metabolism is a key feature of biodiversity that remains underexploited in functional frameworks used in agroecology. Here, we study how phytochemical diversity considered at three organizational levels can promote pest control. In a factorial field experiment, we manipulated plant diversity in three monocultures and three mixed crops of oilseed rape to explore how intra- and interspecific phytochemical diversity affects pest infestation. We combined recent progress in metabolomics with classic metrics used in ecology to test a box of hypotheses grounded in plant defence theory. According to the hypothesis of ‘phytochemically mediated coevolution’, our study stresses the relationships between herbivore infestation and particular classes of specialized metabolites like glucosinolates. Among 178 significant relationships between metabolites and herbivory rates, only 20% were negative. At the plant level, phytochemical abundance and richness had poor predictive power on pest regulation. This challenges the hypothesis of ‘synergistic effects
’
. At the crop cover level, in line with the hypothesis of ‘associational resistance’, the phytochemical dissimilarity between neighbouring plants limited pest infestation. We discuss the intricate links between associational resistance and bottom-up pest control. Bridging different levels of organization in agroecosystems helps to dissect the multi-scale relationships between phytochemistry and insect herbivory.
On the stability of prestressed beams undergoing nonlinear flexural free oscillations
Authors: Di Gregorio Laura , Lacarbonara Walter
Published: July 2024

We study the nonlinear free undamped motions of a hinged-hinged beam exhibiting geometric stretching-induced nonlinearity and arbitrary initial conditions. We treat the governing integral-partial-differential equation of motion as an infinite dimensional Hamiltonian system. We analytically obtain a quantitative Birkhoff Normal Form via a nonlinear coordinate transformation that yields the reduced (modulation) equations describing the free oscillations to within a certain nonlinear order with an estimate of the reminder. The obtained solutions provide a very precise description of small amplitude oscillations over large time scales. The analytical optimization of the involved estimates yields time stability results obtained for plausible values of the physical quantities and of the perturbation parameter. The role played by internal resonances in determining the time stability of the solution is highlighted and discussed. We show that initial conditions with a finite number of eigenfunctions yield bounded solutions living on invariant subspaces of the involved modes at all times. Conversely, initial conditions comprising the full (infinite) spectrum of eigenfunctions provide solutions for which time stability for all times cannot be stated.
Infection–nutrition feedbacks: fat supports pathogen clearance but pathogens reduce fat in a wild mammal
Authors: Smiley Rachel A. , Wagler Brittany L. , Edwards William H. , Jennings-Gaines Jessica , Luukkonen Katie , Robbins Kara , Johnson Marguerite , Courtemanch Alyson B. , Mong Tony W. , Lutz Daryl , McWhirter Doug , Malmberg Jennifer L. , Lowrey Blake , Monteith Kevin L.
Published: July 2024

Though far less obvious than direct effects (clinical disease or mortality), the indirect influences of pathogens are difficult to estimate but may hold fitness consequences. Here, we disentangle the directional relationships between infection and energetic reserves, evaluating the hypotheses that energetic reserves influence infection status of the host and that infection elicits costs to energetic reserves. Using repeated measures of fat reserves and infection status in individual bighorn sheep (
Ovis canadensis
) in the Greater Yellowstone Ecosystem, we documented that fat influenced ability to clear pathogens (
Mycoplasma ovipneumoniae
) and infection with respiratory pathogens was costly to fat reserves. Costs of infection approached, and in some instances exceeded, costs of rearing offspring to independence in terms of reductions to fat reserves. Fat influenced probability of clearing pathogens, pregnancy and over-winter survival; from an energetic perspective, an animal could survive for up to 23 days on the amount of fat that was lost to high levels of infection. Cost of pathogens may amplify trade-offs between reproduction and survival. In the absence of an active outbreak, the influence of resident pathogens often is overlooked. Nevertheless, the energetic burden of pathogens likely has consequences for fitness and population dynamics, especially when food resources are insufficient.
Chemical defences indicate bold colour patterns with reduced variability in aposematic nudibranchs
Authors: van den Berg Cedric P. , Santon Matteo , Endler John A. , Drummond Leon , Dawson Bethany R. , Santiago Carl , Weber Nathalie , Cheney Karen L.
Published: July 2024

The selective factors that shape phenotypic diversity in prey communities with aposematic animals are diverse and coincide with similar diversity in the strength of underlying secondary defences. However, quantitative assessments of colour pattern variation and the strength of chemical defences in assemblages of aposematic species are lacking. We quantified colour pattern diversity using quantitative colour pattern analysis (QCPA) in 13 dorid nudibranch species (Infraorder: Doridoidei) that varied in the strength of their chemical defences. We accounted for the physiological properties of a potential predator’s visual system (a triggerfish,
Rhinecanthus aculeatus
) and modelled the appearance of nudibranchs from multiple viewing distances (2 and 10 cm). We identified distinct colour pattern properties associated with the presence and strength of chemical defences. Specifically, increases in chemical defences indicated increases in colour pattern boldness (i.e. visual contrast elicited via either or potentially coinciding chromatic, achromatic and/or spatial contrast). Colour patterns were also less variable among species with chemical defences when compared to undefended species. Our results indicate correlations between secondary defences and diverse, bold colouration while showing that chemical defences coincide with decreased colour pattern variability among species. Our study suggests that complex spatiochromatic properties of colour patterns perceived by potential predators can be used to make inferences on the presence and strength of chemical defences.
Human Metapneumovirus (hMPV): An associated etiology of Severe Acute Respiratory Infection in Children of Eastern Uttar Pradesh, India.
Authors: Deval Hirawati , Kumar Niraj , Srivastava Mitali , Potdar Varsha , Mehta Anita , Verma Ayushi , Singh Rajeev , Kavathekar Asif , Kant Rajni , Murhekar Manoj
Published: July 2024

Acute respiratory infections (ARIs) are a serious public health concern across the world, causing considerable morbidity and mortality. Every year, around 13 million children under the age of five die. Approximately 95% of them are from developing nations, and ARIs are responsible for one-third of all deaths. Human Metapneumovirus (hMPV) is one of the causative agents associated with respiratory tract infections. There is lack of information about hMPV from the eastern region of Uttar Pradesh. In our centre, Indian Council of Medical Research- Regional Medical Research Centre Gorakhpur (ICMR‐RMRC Gorakhpur) at Gorakhpur, Uttar Pradesh, India; we tested for respiratory pathogens in under-five patients presenting with ARI and severe acute respiratory illness (SARI) through semi nested PCR. A total of 100 nasal and throat specimens were collected from the OPD and IPD of Department of Paediatrics, BRD Medical College, Gorakhpur during from February 2022 to April 2022. Out of 100 enrolled pediatric patients, 4 (4%) were found to be positive. Among the patients who tested positive for hMPV, 25% (1/4) patient unfortunately died. The phylogenetic analysis of hMPV showed the close resemblance with the clade of Singapore and USA hMPV isolates. Our work underlines the importance of hMPV as the cause of acute respiratory infections in children and the need for routine testing for this virus in laboratories. Further comprehensive information regarding the incidence of hMPV in this area is needed.
Machine learning-based mortality prediction models for non-alcoholic fatty liver disease in the general United States population
Authors: Zheng Jia-Rui , Wang Zi-Long , Feng Bo
Published: July 2024

Background & Aims

Nowadays, the global prevalence of non-alcoholic fatty liver disease (NAFLD) has reached about 25%, which is the most common chronic liver disease worldwide, and the mortality risk of NAFLD patients is higher. Our research created five machine learning (ML) models for predicting overall mortality in ultrasound-proven NAFLD patients and compared their performance with conventional non-invasive scoring systems, aiming to find a generalizable and valuable model for early mortality prediction in NAFLD patients.

Methods

National Health and Nutrition Examination Survey (NHANES)-III from 1988 to 1994 and NHANES-III related mortality data from 2019 were used. 70% of subjects were separated into the training set (N = 2262) for development, while 30% were in the testing set (N= 971) for validation. The outcome was all-cause death at the end of follow-up. Twenty-nine related variables were trained as predictor features for five ML–based models: Logistic regression (LR), K-nearest neighbors (KNN), Gradient-boosted decision tree (XGBoost), Random forest (RF) and Decision tree. Five typical evaluation indexes including area under the curve (AUC), F1 score, accuracy, sensitivity and specificity were used to measure the prediction performance.

Results

3233 patients with NAFLD in total were eligible for the inclusion criteria, with 1231 death during the average 25.3 years follow up time. AUC of the LR model in predicting the mortality of NAFLD was 0.888 (95% confidence interval [CI] 0.867-0.909), the accuracy was 0.808, the sensitivity was 0.819, the specificity was 0.802, and the F1 score was 0.765, which showed the best performance compared with other models (AUC were: RF, 0.876 [95%CI 0.852-0.897]; XGBoost, 0.875 [95%CI 0.853-0.898]; Decision tree, 0.793 [95%CI 0.766-0.819] and KNN, 0.787 [95%CI 0.759-0.816]) and conventional clinical scores (AUC were: Fibrosis-4 Score (FIB-4), 0.793 [95%CI 0.777-0.809]; NAFLD fibrosis score (NFS), 0.770 [95%CI 0.753-0.787] and aspartate aminotransferase-to-platelet ratio index (APRI), 0.522 [95%CI 0.502-0.543]).

Conclusions

ML–based models, especially LR model, had better discrimination performance in predicting all-cause mortality in patients with NAFLD compared to the conventional non-invasive scores, and an interpretable model like Decision tree, which only used three predictors: age, systolic pressure and glycated hemoglobin, is simple to use in clinical practice.
Coordinated Response Modulations Enable Flexible Use of Visual Information
Authors: Srinath Ramanujan , Czarnik Martyna M. , Cohen Marlene R.
Published: July 2024

We use sensory information in remarkably flexible ways. We can generalize by ignoring task-irrelevant features, report different features of a stimulus, and use different actions to report a perceptual judgment. These forms of flexible behavior are associated with small modulations of the responses of sensory neurons. While the existence of these response modulations is indisputable, efforts to understand their function have been largely relegated to theory, where they have been posited to change information coding or enable downstream neurons to read out different visual and cognitive information using flexible weights. Here, we tested these ideas using a rich, flexible behavioral paradigm, multi-neuron, multi-area recordings in primary visual cortex (V1) and mid-level visual area V4. We discovered that those response modulations in V4 (but not V1) contain the ingredients necessary to enable flexible behavior, but not via those previously hypothesized mechanisms. Instead, we demonstrated that these response modulations are precisely coordinated across the population such that downstream neurons have ready access to the correct information to flexibly guide behavior without making changes to information coding or synapses. Our results suggest a novel computational role for task-dependent response modulations: they enable flexible behavior by changing the information that gets out of a sensory area, not by changing information coding within it.

Significance

Natural perceptual judgments are continuous, generalized, and flexible. We estimate the ripeness of a piece of fruit on a continuous scale, we generalize by judging the ripeness of either a mango or an avocado even though they look very different, we flexibly judge either the size or the ripeness of the same piece of fruit, and we can flexibly indicate the same perceptual judgment using a variety of behaviors such as by speaking or writing any of many languages. Here, we show that the response modulations in visual cortex long associated with cognitive processes, surround modulation, or motor planning are sufficient to guide all these aspects of natural perceptual decision-making. We find that across the population, these response modulations reorient and reformat visual representations so that the relevant information is used to guide behavior via communication with downstream neurons. Our results are an example of a general computational principle for flexible behavior that emerges from the coordinated activity of large populations of neurons.
Flower visitation through the lens: Exploring the foraging behaviour ofBombus terrestriswith a computer vision-based application
Authors: Varga-Szilay Zsófia , Szövényi Gergely , Pozsgai Gábor
Published: July 2024

To understand the processes behind pollinator declines, and thus to maintain pollination efficiency, we also have to understand fundamental drivers influencing pollinator behaviour. In this study, we aim to explore the foraging behaviour of wild bumblebees, recognizing its importance from economic and conservation perspectives. We recordedBombus terrestrisonLotus creticus,Persicaria capitata, andTrifolium pratensepatches in five-minute-long slots in urban areas of Terceira (Azores, Portugal). For the automated bumblebee detection, we created computer vision models based on a deep learning algorithm, with custom datasets. We achieved high F1 scores of 0.88 forLotusandPersicaria, and 0.95 forTrifolium, indicating accurate bumblebee detection. We found that flower cover per cent, but not plant species, influenced the attractiveness of flower patches, with a significant positive effect. There were no differences between plant species in the attractiveness of the flower heads. The handling time was longer on the large-headedTrifoliumthan those on the smaller-headedLotusandPersicaria. However, our result did not indicate significant differences in the time bumblebees spent on flowers among the three plant species. Here, we also justify computer vision-based analysis as a reliable tool for studying pollinator behavioural ecology.
3D micropatterned traction force microscopy: a technique to control three-dimensional cell shape while measuring cell-substrate force transmission.
Authors: Faure Laura M , Gomez Gonzalez Manuel , Baguer Ona , Comelles Jordi , Martinez Elena , Arroyo Marino , Trepat Xavier , Roca-Cusachs Pere
Published: July 2024

Cell shape and function are intimately linked, in a way that is mediated by the forces exerted between cells and their environment. The relationship between cell shape and forces has been extensively studied for cells seeded on flat 2-dimensional (2D) substrates, but not for cells in more physiological three-dimensional (3D) settings. Here, we demonstrate a technique called 3D micropatterned traction force microscopy (3D-μTFM) to confine cells in three-dimensional wells of defined shape, while simultaneously measuring the forces transmitted between cells and their microenvironment. This technique is based on the 3D micropatterning of polyacrylamide wells and on the calculation of 3D traction force from their deformation. With 3D-μTFM, we show that MCF10A breast epithelial cells exert defined, reproducible patterns of forces on their microenvironment, which can be both contractile and extensile. We further show that cells switch from a global contractile to extensile behaviour as their volume is reduced. Our technique enables the quantitative study of cell mechanobiology with full access to 3D cellular forces while having accurate control over cell morphology and the mechanical conditions of the microenvironment.
H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration
Authors: Bernardo-Colón Alexandra , Bighinati Andrea , Parween Shama , Debnath Subrata , Piano Ilaria , Adani Elisa , Corsi Francesca , Gargini Claudia , Vergara Natalia , Marigo Valeria , Becerra S. Patricia
Published: July 2024

Photoreceptor death causes blinding inheritable retinal diseases, such as retinitis pigmentosa (RP). As disease progression often outpaces therapeutic advances, finding effective treatments is urgent. This study focuses on developing a targeted approach by evaluating the efficacy of small peptides derived from pigment epithelium-derived factor (PEDF), known to restrict common cell death pathways associated with retinal diseases. Peptides with affinity for the PEDF receptor, PEDF-R, (17-mer and H105A) delivered via eye drops reached the retina, efficiently promoted photoreceptor survival, and improved retinal function in RP mouse models based on both therd10mutation and the rhodopsin P23H mutation. Additionally, intravitreal delivery of AAV-H105A vectors delayed photoreceptor degeneration in the latter RP mouse model. Furthermore, peptide H105A specifically prevented photoreceptor death induced by oxidative stress, a contributing factor to RP progression, in human retinal organoids. This promising approach for peptide eye drop delivery holds significant potential as a therapeutic for preventing photoreceptor death in retinal disorders, offering a high safety profile, low invasiveness and multiple delivery options.

One Sentence Summary

Neurotrophic PEDF peptides delivered as eye drops preserve photoreceptor viability, morphology, and function in models of human retinal diseases.
Physical Exercise Improves Working Memory through Ripple-Spindle Coupling
Authors: Che Xinyun , Auer Benedikt , Schmid Paul , Reichert Christoph , Scholz Annemarie , Weischner Tom , Knight Robert T. , Dürschmid Stefan
Published: July 2024

Spindle-ripple coupling enhances memory consolidation during sleep. Ripples, representing the compressed reactivation of environmental information, provide a mechanism for retaining memory information in chronological order and are also crucial for working memory (WM) during wakefulness. Brief sessions of physical exercise (PE) are proposed to boost WM. In concurrent EEG/MEG sessions, we investigated the role of PE in WM performance and high-frequency-ripple to spindle coupling. Ripples, identified in MEG sensors covering the medial temporal lobe (MTL) region, predicted individual WM performance. Ripples were locked to robust oscillatory patterns in the EEG defined spindle band. Spindle activity and ripples decrease during initial stimulus presentation and rebound after 1 sec. Behaviorally, PE enhanced WM performance. Neurophysiologically, PE scaled the ripple rate with the number of items to be kept in WM and strengthened the coupling between ripple events and spindle oscillations. These findings reveal that PE enhances WM by coordinating ripple-spindle interaction.
Preclinical validation and kinetic modelling of the SV2A PET ligand [18F]UCB-J in mice
Authors: Everix Liesbeth , Elvas Filipe , Menchaca Alan Miranda , Khetarpal Vinod , Liu Longbin , Bard Jonathan , Staelens Steven , Bertoglio Daniele
Published: July 2024

Synaptic vesicle protein 2A (SV2A) is ubiquitously expressed in presynaptic terminals where it functions as a neurotransmission regulator protein. Synaptopathy has been reported during healthy ageing and in a variety of neurodegenerative diseases. Positron emission tomography (PET) imaging of SV2A can be used to evaluate synaptic density. The PET ligand [11C]UCB-J has high binding affinity and selectivity for SV2A but has a short physical half-life due to the11C isotope. Here we report the characterization and validation of its18F-labeled equivalent, [18F]UCB-J, in terms of specificity, reproducibility and stability in C57BL/6J mice. Plasma analysis revealed at least one polar radiometabolite. Kinetic modelling was performed using a population-based metabolite corrected image-derived input function (IDIF). [18F]UCB-J showed relatively fast kinetics and a reliable measure of the IDIF-based volume of distribution (VT(IDIF)). [18F]UCB-J specificity for SV2A was confirmed through a levetiracetam blocking assay (50 to 200 mg/kg). Reproducibility of theVT(IDIF)was determined through test-retest analysis, revealing significant correlation (r2=0.773,p<0.0001). Time-stability analyses indicate a scan duration of 60 min to be sufficient to obtain a reliableVT(IDIF). In conclusion, [18F]UCB-J is a selective SV2A ligand with optimal kinetics in mice. Further investigation is warranted for (pre)clinical applicability of [18F]UCB-J in synaptopathies.
The Microbiota of Moon Snail Egg Collars is Shaped by Host-Specific Factors
Authors: Piedl Karla , Aylward Frank O. , Mevers Emily
Published: July 2024

Moon Snails lay eggs using a mixture of mucus and sediment to form an egg mass commonly referred to as an egg collar. These collars do not appear to experience micro-biofouling or predation and this observation led us to hypothesize that the egg collars possess a chemically-rich microbiota that protect the egg collars from pathogens. Herein, we sought to gain an understanding of the bacterial composition of the egg collars by amplifying and sequencing the 16S rRNA gene from egg collar and sediment samples collected at four distinct geographical regions in SW Florida. Relative abundance and non-metric multidimensional scaling plots revealed distinct differences in the bacterial composition between the egg collar and sediment samples. In addition, the egg collars had a lower α-diversity than the sediment, with specific genera being significantly enriched in the egg collars. Analysis of microorganisms consistent across two seasons suggests thatFlavobacteriaceaemake up a large portion of the core microbiota (36 – 58% of 16S sequences). We also investigated the natural product potential of the egg collar microbiota by sequencing a core biosynthetic gene, the adenylation domains (AD), within the gene clusters of non-ribosomal peptide synthetase (NRPS). AD sequences matched multiple modules within known bioactive NRPs biosynthetic gene clusters, suggesting production is possible within the egg collar system and lays the foundation for future studies into the chemical and ecological role of this microbiota.

IMPORTANCE

Animals commonly partner with microorganisms to accomplish essential tasks, including chemically defending the animal host from predation and/or infections. Understanding animal-microbe partnerships and the molecules used by the microbe to defend the animals from pathogens or predation have the potential to lead to new pharmaceutical agents. However, very few of these systems have been investigated. A particularly interesting system are nutrient rich marine egg collars, which often lack visible protections, and are hypothesized to harbor beneficial microbes that protect the eggs. In this study, we gained an understanding of the bacterial strains that form the core microbiota of Moon Snail egg collars and gained a preliminary understanding of their natural product potential. This work lays the foundation for future work to understand the ecological role of the core microbiome and to study the molecules involved in chemically defending the Moon Snail eggs.
Limited protection against early-life cytomegalovirus infection results from deficiency of cytotoxic CD8 T cells
Authors: Brito Luís Fonseca , Ostermann Eleonore , Perez Anna , Tödter Silvia , Virdi Sanamjeet , Indenbirken Daniela , Glau Laura , Gieras Anna , Brixel Renke , Arens Ramon , Grundhoff Adam , Arck Petra , Diemert Anke , Tolosa Eva , Brune Wolfram , Stahl Felix Rolf
Published: July 2024

Differential antiviral T cell immunity in early life impacts the clinical outcome of Cytomegalovirus (CMV) infection, but the underlying mechanisms are not well understood. Here, we found delayed enrichment of early-life murine CMV-specific CD8 T cells due to a general deficiency of αβ T cells. Adoptive transfer of naïve adult T cells into neonates did not protect due to a blockade of CD8 but not of CD4 effector T cell differentiation. Early-life deficiency of critical signal 3 cytokines during T cell priming resulted in the appearance of non-cytotoxic CD8 effector T cells whereas the effector phase of adult-primed T cells was not disrupted in neonates. Accordingly, we found an overall low number of antiviral human CD8 T cells in newborns with congenital CMV. Together, this study suggests defective CD8 T cell immunity as an important factor explaining the higher risk for CMV disease in the early-life phase.
Diverse Genomic Embedding Benchmark for functional evaluation across the tree of life
Authors: West-Roberts Jacob , Kravitz Joshua , Jha Nishant , Cornman Andre , Hwang Yunha
Published: July 2024

Biological foundation models hold significant promise for deciphering complex biological functions. However, evaluating their performance on functional tasks remains challenging due to the lack of standardized benchmarks encompassing diverse sequences and functions. Existing functional annotations are often scarce, biased, and susceptible to train-test leakage, hindering robust evaluation. Furthermore, biological functions manifest at multiple scales, from individual residues to large genomic segments. To address these limitations, we introduce the Diverse Genomic Embedding Benchmark (DGEB), inspired by natural language embedding benchmarks. DGEB comprises six embedding tasks across 18 expert curated datasets, spanning sequences from all domains of life and encompassing both nucleic acid and amino acid modalities. Notably, four datasets enable direct comparison between models trained on different modalities. Benchmarking protein and genomic language models (pLMs and gLMs) on DGEB reveals performance saturation with model scaling on numerous tasks, especially on those with underrepresented sequences (e.g. Archaea). This highlights the limitations of existing modeling objectives and training data distributions for capturing diverse biological functions. DGEB is available as an open-source package with a public leaderboard athttps://github.com/TattaBio/DGEB.
Welcome to Hotel Hymenoptera: monitoring cavity-nesting bee and wasp distribution and their trophic interactions using community science and metabarcoding
Authors: Handler Sage , Coveny Katerina , Braukmann Thomas , Raine Nigel E. , Steinke Dirk
Published: July 2024

Essential ecosystem services are provided by many interactions, including plant-pollinator, predator-prey, and host-parasitoid. These services support food and natural systems through pollination and pest control, however they are challenging to qualify, and previous observational studies may underestimate their complexity. The cavity nesting Hymenoptera are a good example showing all these three interactions and they can be monitored using trap nests. For this study, trap nests were installed at schools across Canada by community scientists to investigate cavity-nesting bee and wasp distributions and interactions. DNA metabarcoding was used to identify the occupants and their food sources. New bee and wasp distributions were found that might be the result of previous under-sampling or recent range expansions. Detailed bipartite and tripartite networks describing species interactions suggest some novel bee, wasp, and parasite associations. These results encourage further investigation into these interactions using molecular methods as detailed range maps and networks provide information to natural historians and conservationists alike.
Metacollinia emscherin. sp., a novel sanguicolous apostome ciliate of freshwater amphipods (Gammarusspp.)
Authors: Prati Sebastian , Rückert Sonja , Grabner Daniel S. , Sures Bernd , Bojko Jamie
Published: July 2024

We describe a novel sanguicolous parasitic ciliate,Metacollinia emscherin. sp., found in the freshwater amphipodsGammarus pulexandG. fossarum. This ciliate infected up to 20% of the amphipods collected in a German stream catchment, the Boye, a tributary of the river Emscher. The ciliate showed morphological characteristics fitting the genusMetacollinia. Different life stages of variable size occurred simultaneously in the hemocoel throughout the hosts’ body. The tomont had 40-47 slightly spiraled kineties, a non-ciliated cortical band, a large macronucleus, and contractile vacuoles arranged in rows or scattered throughout the cytoplasm. The protomites/tomites with nine somatic kineties presented evidence of the buccal kineties x, y, and z reminiscent of those of the order Foettingeriida. Phylogenetic analyses of the 18S rRNA and COI regions confirm the ciliate placement in the Collinidae and a close relatedness to the type species of the genusMetacollinia,Metacollinia lucensis.

We formally describe this new parasite asMetacollinia emscherin. sp. using pathological, morphological, and nuclear/mitochondrial genetic data. The systemic infections observed in histological preparations and the pathogenicity ofMetacollinia emscherin. sp. suggest that this parasite might influence host population dynamics. Given the ecological importance of amphipods as keystone species in freshwater ecosystems, an outbreak of this parasite might indirectly impact ecosystem functioning.
Forecasting the Effects of Global Change on a Bee Biodiversity Hotspot
Authors: Buckner Mark A. , Hoge Steven T. , Danforth Bryan N.
Published: July 2024

The Mojave and Sonoran Deserts, recognized as a global hotspot for bee biodiversity, are experiencing habitat degradation from urbanization, utility-scale solar energy (USSE) development, and climate change. In this study, we evaluated the current and future distribution of bee diversity in the region, assessed how protected areas safeguard bee species richness, and predicted how global change may affect bees across the region. Using Joint Species Distribution Models (JSDMs) of 148 bee species, we project changes in species distributions, occurrence area, and richness across the region under four global change scenarios between 1971 and 2050. We evaluated the threat posed by USSE development and predicted how climate change will affect the suitability of protected areas for conservation. Our findings indicate that changes in temperature and precipitation do not uniformly affect bee richness across the region. Protected areas in the Sonoran and Mojave Deserts are projected to experience mean losses of up to 5.8 species, whereas protected areas at higher elevations and transition zones may gain up to 7.8 species. Outside protected areas, bee diversity is threatened by urbanization and USSE development. Areas prioritized for future USSE development have an average species richness of 4.2 species higher than the study area average, and lower priority areas have 8.2 more species. USSE zones are expected to experience declines of 2.7 to 8.0 species by 2050 due to climate change alone. Despite the importance of solitary bees for pollination, their diversity is often overlooked in land management decisions. Our results show the utility of JSDMs for extending the usability of existing data-limited bee species records, easing the inclusion of these species in conservation and land management decision-making. The multiple threats from global change drivers underscore the importance of including ecologically vital, though often data-limited, species in land-use decisions.
Diet-induced obesity mediated through Estrogen-Related Receptor α is independent of intestinal function
Authors: Vemuri Kiranmayi , Iqbal Jahangir , Kumar Sneha , Logerfo Alexandra , Verzi Michael P.
Published: July 2024

Obesity has become an epidemic, prompting advances in therapies targeting this condition. Estrogen-related receptor α (ESRRA), a transcription factor, plays pivotal roles in energy metabolism across diverse tissues. Studies have demonstrated that loss ofEsrraleads to fat malabsorption and resistance to diet-induced obesity. However, the reliance of these studies on germlineEsrramutants overlooks the tissue-specific implications of ESRRA in diet-induced obesity. Notably,Esrraexhibits high expression in the gastrointestinal (GI) tract relative to other tissues. Given the critical role of the GI tract in dietary lipid metabolism, this study employs mouse genetics and genomics approaches to dissect the specific impact of intestinal ESRRA along with investigating its role in diet-induced obesity.

Data Transparency

ChIP-seq and RNA-seq data from this publication have been deposited to GEO accession numbers GSE269824 and GSE269825, respectively. Any additional information required to reanalyze the data reported in this paper is available from the corresponding author upon request.

Grant Support

This research was funded by grants from the National Institutes of Health (NIH) to M.P.V. (R01DK121915 and R01DK126446). K.V. was supported by an American Heart Association pre-doctoral fellowship (906006). S.K. was supported by a Rutgers DLS Summer Undergraduate Research Fellowship. A.L. was supported by grants from the NIH grant F31DK137596 and the NIH T32 Biotechnology Training Program (GM135141). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Disclosures

The authors declare no competing interests.
MAGE-A4-Responsive Plasma Cells Promote Non-Small Cell Lung Cancer
Authors: Armstrong Dominique , Chang Cheng-Yen , Hong Monica J. , Green Linda , Hudson William , Shen Yichao , Song Li-Zhen , Jammi Sheetal , Casal Benjamin , Creighton Chad J. , Carisey Alexandre , Zhang Xiang H.-F. , McKenna Neil J. , Kang Sung Wook , Lee Hyun-Sung , Corry David B. , Kheradmand Farrah
Published: July 2024

Adaptive immunity is critical to eliminate malignant cells, while multiple tumor-intrinsic factors can alter this protective function. Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, is expressed in several solid tumors and correlates with poor survival in non-small cell lung cancer (NSCLC), but its role in altering antitumor immunity remains unclear. We found that expression of MAGE-A4 was highly associated with the loss ofPTEN, a tumor suppressor, in human NSCLC. Here we show that constitutive expression of humanMAGE-A4combined with the loss ofPtenin mouse airway epithelial cells results in metastatic adenocarcinoma enriched in CD138+CXCR4+plasma cells, predominantly expressing IgA. Consistently, human NSCLC expressing MAGE-A4 showed increased CD138+IgA+plasma cell density surrounding tumors. The abrogation of MAGE-A4-responsive plasma cells (MARPs) decreased tumor burden, increased T cell infiltration and activation, and reduced CD163+CD206+macrophages in mouse lungs. These findings suggest MAGE-A4 promotes NSCLC tumorigenesis, in part, through the recruitment and retention of IgA+MARPs in the lungs.
Use of Nicotine Products, Prescription Drug Products, and Other Methods to Stop Smoking by US Adults in the 2022 National Health Interview Survey
Authors: Foxon Floe , Niaura Raymond
Published: July 2024

Recent data on methods used by adults to stop smoking can inform tobacco control policies. Nationally representative Centers for Disease Control and Prevention survey data from the 2022 National Health Interview Survey (N=27,651) were used to analyze populations of US adults who self-reported having stopped smoking cigarettes for 6 months or longer in the last year and the methods they used, or who did not stop smoking but tried in the last year (n=1,735). In 2022, an estimated 2.9 million [95% CI:2.5 million–3.2 million] US adults had stopped smoking in the past year. Most were male, non-Hispanic White, aged <55 years, college-educated, identified as straight, were not depressed, and currently drank alcohol. The most popular methods used to stop smoking were nicotine products (53.9% [47.4%–60.3%]; 1.5 [1.3– 1.8] million adults), especially e-cigarettes in combination with other methods (40.8% [34.4%– 47.5%]; 1.2 [0.9–1.4] million) and e-cigarettes alone (26.0% [20.4%–32.3%]; 0.7 [0.6–0.9] million). Prescription drug products (8.1% [5.3%–11.8%]; 0.2 [0.1–0.3] million) and non-nicotine, non-prescription drug methods (6.3% (3.9%–9.7%); 0.2 [0.1–0.3] million) were less popular. A further 13.1 [12.2–14.0] million tried but did not stop smoking. Compared to those who tried but didn’t stop smoking, those who successfully stopped were more likely to be younger, degree-educated, and to use e-cigarettes to stop smoking. Many adults still attempt to stop smoking unaided. Interventions to reduce smoking could focus on populations that stopped smoking the least and encourage use of evidence-based methods.
Left atrial wall shear stress distribution correlates with atrial endocardial electrogram voltage and fibrosis in patients with atrial fibrillation
Authors: Adamopoulos Dionysios , Rovas Georgios , Johner Nicolas , Müller Hajo , Deux Jean-François , Crowe Lindsey A. , Vallée Jean-Paul , Mach François , Stergiopulos Nikolaos , Shah Dipen
Published: July 2024

Left atrial (LA) wall fibrosis plays an important role in the perpetuation of atrial fibrillation (AF) since the abnormal electrophysiological properties of the fibrotic areas sustains the arrhythmia by favoring both re-entry circuits as well as abnormal impulse generation. Despite its crucial contribution, the mechanisms by which LA fibrosis develops are not well understood.

The LA wall is constantly exposed to the hydraulic forces exerted by the blood flow arriving from the pulmonary veins. The purpose of the present study was to examine the association between regional wall shear stress and areas with fibrosis in the LA of patients with AF.

15 patients (13 males, mean age 61±11 years) with AF, no significant mitral regurgitation and clinical indication for a primary catheter ablation were prospectively recruited for the study. All participants underwent a baseline three-dimensional electro-anatomical mapping of the LA during the ablation procedure and a pre-interventional cardiovascular magnetic resonance (CMR) imaging with phase contrast for mitral flow estimation and Gadolinium injection for LA fibrosis detection. Fibrotic areas were detected either by low bipolar voltage (BV≤0.5mV) and/or by areas with enhanced late Gadolinium uptake as assessed by the image intensity ratio (IIR≥1.2). For all subjects, a detailed 3D anatomical model of the LA was extracted from the invasive electro-anatomical maps and was used to calculate regional time-averaged wall shear stress (TAWSS) and blood age (BA), an index of blood stagnation, by performing patient-specific computational fluid dynamic simulations.

Globally, areas around the pulmonary veins and the LA roof exhibited the highest values of TAWSS. In all cases, high TAWSS was strongly correlated with low voltage (n=15, r from -0.002 to -0.449, p<0.01) and enhanced late Gadolinium uptake (n=12, r from 0.071 to 0.475, p<0.001). Fibrotic areas as detected by both low BV and high IIR were more prevalent in areas exposed to high TAWSS (21.6% vs 8.1% and 26.2% vs 13.2% respectively, p<0.001). Inversely, in all but one case, areas with low TAWSS presented more intense blood stagnation as assessed by the highest BA (r from -0.268 to - 0.688, p<0.001).

In patients with AF, regional high TAWSS is associated with corresponding CMR biomarkers of left atrial wall fibrosis and electrical scaring. Inversely, areas with low TAWSS are associated with blood stagnation and could favor thrombus formation. This may provide insights of a novel pathophysiological mechanism explaining the characteristic atrial electrical remodeling and thrombus formation seen in patients with AF.
Deficiencies in accessibility to point-of-care (POC) diagnostics in PMTCT services in rural primary health care clinics in Zambia: Implementation Science perspective
Authors: Katoba J
Published: July 2024

Introduction

Point-of-care (POC) innovations are healthcare interventions that have great potential to improve diagnostic capacities of healthcare systems in low- and middle-income countries (LMICs). From the implementation science perspective, this study explores perceptions of key stakeholders on deficiencies in accessibility of POC diagnostics in the context of prevention of mother-to-child transmission (PMTCT) services in Zambia.

Methods

A retrospective qualitative evaluation was conducted to understand factors that influence POC diagnostic implementation in rural primary healthcare (PHC) settings. The study was conducted among key implementing stakeholders in Zambia. In-depth interviews were held with 11 purposefully selected key informants, including clinical officers, midwives, nurses, environmental health technicians (EHTs), government and private health officials. The interviews were audio-recorded and transcribed verbatim. Following coding, thematic content analysis was applied and the main emerging themes were analysed through the lens of the Consolidated Framework for Implementation Research (CFIR). The CFIR was identified as the most appropriate model to interpret our findings.

Results

Factors influencing implementation were represented in all five domains. Major constructs as facilitators were the relative advantage of the intervention, external partnership, education and training, knowledge and belief, self-efficacy, and engagement of champions. Barriers were mainly found in the outer and inner settings, including constraints in financial resources, supply chain challenges resulting in stock-outs, insufficient human resources leading to increased workload, and other infrastructural issues like space limitations and lack of electricity in most rural primary healthcare settings.

Conclusions

The study identified key determinants that supported or hindered the implementation of POC diagnostics in the rural PHCs. Greater efforts are needed to overcome barriers at multi-sectoral level for effective implementation while leveraging on facilitators through a health system strengthening approach. These findings are key to informing future implementations, sustainability and scale-up of POC diagnostics interventions.
Changing feeding levels reveal plasticity in elasmobranch life history strategies
Authors: Lucas Sol , Berggren Per , Barrowclift Ellen , Smallegange Isabel M.
Published: July 2024

Life history strategies are shaped by phylogeny, environmental conditions and individual energy budgets, and have implications for population performance. Here, we used an approach that merges demography with energy budget theory to structure life history traits of 151 elasmobranch species into life history strategies for two contrasting feeding levels. We assessed how phylogeny and habitat impacted life history strategies, and tested if these strategies predict population performance and conservation status. Elasmobranch life history strategies are structured along the fast-slow continuum and reproductive strategy axes. However, species’ positions in this life history space were not fixed, but instead moved in an anticlockwise ‘whirlpool’ manner along the two axes in response to an increase in feeding level. We also found that population growth rate does not necessarily inform on a species demographic resilience. Finally, only at the higher feeding level does the fast-slow continuum predict IUCN conservation status, with the slowest species at the highest risk of extinction. Our analyses reveal plasticity in species life history strategies, and warn against extrapolating the fast-slow continuum and reproductive strategy framework from one environment to another when predicting a species’ response to (climate) change, perturbations, and, particularly in case of elasmobranchs, (over)exploitation.
Comparative evaluation of four exome enrichment solutions in 2024: Agilent, Roche, Vazyme and Nanodigmbio
Authors: Belova Vera , Vasiliadis Iuliia , Repinskaia Zhanna , Samitova Alina , Shmitko Anna , Ponikarovskaya Natalya , Suchalko Oleg , Cheranev Valery , Peter Shatalov , Peter Shegai , Andrey Kaprin , Rebrikov Denis , Korostin Dmitriy
Published: July 2024

Whole exome sequencing (WES) is essential for identifying genetic variants linked to diseases. This study compares available to date four exome enrichment kits: Agilent SureSelect Human All Exon v8, Roche KAPA HyperExome Probes, Vazyme VAHTS Target Capture Core Exome Panel, and Nanodigmbio NEXome Plus Panel v1. We evaluated target design, coverage statistics, and variant calling accuracy across these four different exome capture products. All kits showed high coverage completeness, with mean x10 coverage exceeding 97.5% and x20 coverage above 95%. Roche exhibited the most uniform coverage, indicated by the lowest fold-80 scores, while Nanodigmbio had more on-target reads due to fewer off-target reads. Variant calling performance, evaluated using in-lab standard E701 DNA sample, showed high recall rates for all kits, especially Agilent v8. All kits achieved an F-measure above 95.87%. Nanodigmbio had the highest precision with the fewest false positives but a slightly lower F-measure than other kits. This study also highlights the performance of new Chinese solutions from Vazyme and Nanodigmbio, which were comparable to Agilent v8 and Roche KAPA kits. These findings assist researchers and clinicians in selecting appropriate exome capture solutions.
Gut-specific H3R signaling orchestrates microglia-dependent resolution of peripheral inflammation
Authors: Dürholz Kerstin , Linnerbauer Mathias , Schmid Eva , Danzer Heike , Lößlein Lena , Amend Lena , Ehnes Leona , Frech Michael , Azizov Vugar , Schälter Fabian , Gessner Arne , Lucas Sébastien , Lesker Till-Robin , Taudte R. Verena , Hofmann Jörg , Beyer Felix , Bootz-Maoz Hadar , Reich Yasmin , Romano Hadar , Mauro Daniele , Beckervordersandforth Ruth , Xiang Wei , Haghikia Aiden , Akdis Cezmi A. , Ciccia Francesco , Bäuerle Tobias , Sarter Kerstin , Strowig Till , Yissachar Nissan , Schett Georg , Rothhammer Veit , Zaiss Mario M.
Published: July 2024

Chronic inflammatory diseases, like rheumatoid arthritis (RA) have been described to cause central nervous system (CNS) activation. Less is known about environmental factors that enable the CNS to suppress peripheral inflammation in RA. Here, we identified gut microbiota-derived histamine as such factor. We show that low levels of histamine activate the enteric nervous system, increase inhibitory neurotransmitter concentrations in the spinal cord and restore homeostatic microglia, thereby reducing inflammation in the joints. Selective histamine 3 receptor (H3R) signaling in the intestine is critical for this effect, as systemic and intrathecal application did not show effects. Microglia depletion or pharmacological silencing of local nerve fibers impaired oral H3R agonist-induced pro-resolving effects on arthritis. Moreover, therapeutic supplementation of the SCFA propionate identified one way to expand local intestinal histamine concentrations in mice and humans. Thus, we define a gut-CNS-joint axis pathway where microbiota-derived histamine initiates the resolution of arthritis via the CNS.

Graphical Abstract

Gut microbiota-derived histamine activates enteric neurons via H3R

Local intestinal H3R activation induces shift to homeostatic microglia in the spinal cord

CNS controlled decrease in endothelial leakiness resolves synovial inflammation