bluuebunny/crossref_metadata_2025 huggingface dataset:
An update on pharyngeal assessment by the modified barium swallow
Authors: Zarzour Jessica , Revels Jonathan , Rao Korivi Brinda , Martin-Harris Bonnie
Published: December 2024

The modified barium swallow study (MBSS) is a diagnostic examination that visualizes the functional anatomy and physiology of the oral pharyngeal swallowing mechanism in real time. The MBSS, a videofluoroscopic imaging method, is indicated for patients with known or suspected oropharyngeal dysphagia and ideally involves the combined expertise of a radiologist and speech pathologist. The MBSS provides critical diagnostic insights that help in identifying and assessing the type and severity of physiological swallowing impairments, evaluating the safety of oral intake, testing the effectiveness of evidence-based interventions, and developing treatment plans. This manuscript aims to present an overview of MBSS standards from an interdisciplinary perspective, emphasizes key areas of best practices, and reviews the common morphologic abnormalities seen on MBSS exams.
Hawking radiation with pure states
Authors: Kumar K. Sravan , Marto João
Published: December 2024

Hawking’s seminal work on black hole radiation highlights a critical issue in our understanding of quantum field theory in curved spacetime (QFTCS), specifically the problem of unitarity loss (where pure states evolve into mixed states). In this paper, we examine a recent proposal for a direct-sum QFTCS, which maintains unitarity through a novel quantization method that employs geometric superselection rules based on discrete spacetime transformations. This approach describes a quantum state in terms of components that evolve within geometric superselection sectors of the complete Hilbert space, adhering to the discrete symmetries of a Schwarzschild black hole. Consequently, it represents a maximally entangled pure state as a direct-sum of two components in the interior and exterior regions of the black hole, thereby preserving the unitarity of Hawking radiation by keeping it in the form of pure states.
The role of hypoxia-inducible factors 1 and 2 in the pathogenesis of diabetic kidney disease
Authors: Kleibert Marcin , Tkacz Kamil , Winiarska Katarzyna , Małyszko Jolanta , Cudnoch-Jędrzejewska Agnieszka
Published: December 2024

According to the 10th edition of the IDF Diabetes Atlas, 537 million people suffered from diabetes in 2021, and this number will increase by 47% by 2045. It is estimated that even 30–40% of these individuals may develop diabetic kidney disease (DKD) in the course of diabetes. DKD is one of the most important complications of diabetes, both in terms of impact and magnitude. It leads to high morbidity and mortality, which subsequently impacts on quality of life, and it carries a high financial burden. Diabetic kidney disease is considered a complex and heterogeneous entity involving disturbances in vascular, glomerular, podocyte, and tubular function. It would appear that hypoxia-inducible factors (HIF)-1 and HIF-2 may be important players in the pathogenesis of this disease. However, their exact role is still not fully investigated. In this article, we summarize the current knowledge about HIF signaling and its role in DKD. In addition, we focus on the possible effects of nephroprotective drugs on HIF expression and activity in various tissues.

Graphical abstract
Fused filament fabrication of polyetheretherketone in vacuum: the influence of high vacuum on layer adhesion in z-orientation
Authors: Kühn-Kauffeldt Marina , Kühn Marvin , Mittermeier Christoph , Kiendl Josef
Published: December 2024

The application of fused filament fabrication (FFF) in vacuum changes the heat transfer of the process. This work investigates the influence of the working ambient pressure conditions in FFF-based 3D printing of polyetheretherketone (PEEK) specimens, and its impact on the resulting part strength. Layer adhesion drastically improves with decreasing pressure, maximum layer adhesion is reached for ambient pressure below $$10^{-3}$$

10

-
3

mbar. We show that simple and low-cost vacuum equipment is sufficient to achieve such pressure conditions, making this process interesting for the general processing of high-temperature polymers using FFF.
Machine Learning Potential for Serpentines
Authors: Wang Hongjin , Luo Chenxing , Wentzcovitch Renata M.
Published: December 2024

Serpentines are layered hydrous magnesium silicates (MgOO) formed through serpentinization, a geochemical process that significantly alters the physical property of the mantle. They are hard to investigate experimentally and computationally due to the complexity of natural serpentine samples and the large number of atoms in the unit cell. We developed a machine learning (ML) potential for serpentine minerals based on density functional theory calculation with the SCAN meta‐GGA functional for molecular dynamics simulation. We illustrate the success of this ML potential model in reproducing the high‐temperature equation of states of several hydrous phases under the Earth's subduction zone conditions, including brucite, lizardite, and antigorite. In addition, we investigate the polysomes of antigorite with periodicity  = 13–24, which is believed to be all the naturally existent antigorite species. We found that antigorite with larger than 21 appears more stable than lizardite at low temperatures. This ML potential can be further applied to investigate more complex antigorite superstructures with multiple coexisting periodic waves.
Genomic landscape of circulating tumor DNA in HER2-low metastatic breast cancer
Authors: Yi Zongbi , Feng Kaixiang , Lv Dan , Guan Yanfang , Shao Youcheng , Ma Fei , Xu Binghe
Published: December 2024

The large population of HER2-low breast cancer patients necessitates further research to provide enhanced clinical guidance. In this study, we retrospectively analyzed 1071 metastatic breast cancer (MBC) patients and the circulating tumor DNA (ctDNA) to investigate clinicopathological and genetic alterations of HER2-low MBC patients. The effect of HER2-low status on different treatment modalities was explored in two prospective clinical trials (NCT03412383, NCT01917279) and a retrospective study. Our findings suggest TP53, PIK3CA, and ESR1 are frequently mutated genes in HER2-low MBC. Compared to the HER2-0 group, mutations observed in the HER2-low group are more closely associated with metabolic pathway alterations. Additionally, among patients with ERBB2 mutations and treated with pyrotinib, the HER2-low group may experience superior prognosis when compared to the HER2-0 group. Notably, we did not find any statistically significant disparity in the response to chemotherapy, endocrine therapy, or CDK4/6 inhibitor therapy between HER2-0 and HER2-low breast cancer patients. Interestingly, within the subgroup of individuals with metabolic pathway-related gene mutations, we found that HER2-low group exhibited a more favorable response to these treatments compared to HER2-0 group. Additionally, dynamic analysis showed the HER2-low MBC patients whose molecular tumor burden index decreased or achieved early clearance of ctDNA after the initial two treatment cycles, exhibited prolonged survival. Moreover, we classified HER2-low MBC into three clusters, providing a reference for subsequent treatment with enhanced precision. Our study offers valuable insights into the biology of HER2-low MBC and may provide reference for personalized treatment strategies.
Anlotinib plus chemotherapy as a first-line treatment for gastrointestinal cancer patients with unresectable liver metastases: a multicohort, multicenter, exploratory trial
Authors: Wu Jun-Wei , Zhou Chen-Fei , Han Zheng-Xiang , Zhang Huan , Yan Jun , Chen Jun , Wang Chun-Bin , Qin Zhi-Quan , Mao Yong , Tang Xin-Yu , Zhu Liang-Jun , Wei Xiao-Wei , Cui Dong-Hai , Yang Xiu-Li , Shi Min , Zhao Li-Qin , Jiang Jin-Ling , Zhu Wei-You , Wang Hong-Mei , Wang Chun , Zhu Ling-Jun , Zhang Jun
Published: December 2024

This multicohort phase II trial (ALTER-G-001; NCT05262335) aimed to assess the efficacy of first-line anlotinib plus chemotherapy for gastrointestinal (GI) cancer patients with unresectable liver metastases. Eligible patients with colorectal cancer (Cohort A) or noncolorectal and nonesophageal GI cancer (Cohort C) received six cycles of anlotinib plus standard chemotherapeutic regimens followed by anlotinib plus metronomic capecitabine as a maintenance therapy. Liver metastasectomy can be performed when liver metastases are converted to resectable lesions. The primary outcome was the investigator-confirmed objective response rate (ORR) in the intention-to-treat population. Among the 47 patients in Cohort A, the ORR was 40.4% (95% CI 26.4–55.7), including 1 with a complete response (CR) and 18 who achieved a partial response (PR). The median progression-free survival (PFS) was 8.7 months (95% CI 7.3-NE), and the median overall survival (OS) was not reached. In Cohort C, 14 of 44 patients achieved a PR, with an ORR of 31.8% (95% CI 18.6–47.6). The PFS and OS were 5.8 months (95% CI 4.8–6.5) and 11.4 months (95% CI 5.8–19.3), respectively. The liver metastasectomy rate in patients with liver-limited disease was 22.7% (5/22) in Cohort A and 6.7% (2/30) in Cohort C. For pancreatic cancer patients, the ORR of the efficacy-evaluable population was 36.0% (9/25), and those with liver-limited metastasis had better survival. Moreover, no new safety concerns emerged. In conclusion, an anlotinib-based first-line regimen demonstrated promising antitumor activity among GI cancer patients with unresectable liver metastases and led to liver metastasectomy in selected patients.
What can echolocation recordings reveal about the species composition, habitat specificity and structure of mangrove bat communities in the Northern Territory?
Authors: McKenzie N. L. , Bullen R. D. , Milne D. J.
Published: December 2024

In June 2021 we used ultrasonic recorders to inventory zoophagic bats at mangrove patches in three bioregions on the Northern Territory coast: Darwin Coastal, Arnhem Coast and Gulf Coastal. All species could be separated in terms of their search-mode echolocation sequences using tropical Western Australian and Northern Territory reference libraries based on pulse peak frequency (Fpeak), fineness-of-tuning (Q−6dB), repetition-rate and shape. Twenty-five of the 27 species that comprise the ‘Top End’ zoophagic bat fauna are now known to occur in its mangroves, an average of 21.3 ± 0.3 (s.e.) species per bioregion. Northern Territory and Western Australian populations of all but three species show few discernable differences in the four echolocation metrics assessed. Unlike the tropical bioregions in Western Australia, no bat species is confined to mangroves in the Northern Territory. Even so, analysis of data from these and adjacent bioregions shows that bat community structures throughout tropical north-western Australia are adapted to their environmental setting.
Using stable-isotope analysis to assess recent diet and habitat use of stranded green turtles (Chelonia mydas)
Authors: Glen Joshua J. , Buelow Christina A. , Campbell Max D. , Day Joanna , Meagher Phoebe J. B. , van de Merwe Jason P. , Pearson Ryan M.
Published: December 2024

Context Gaining a better understanding of the foraging ecology of green turtles (Chelonia mydas) in different regions can improve the effectiveness of conservation and management strategies for this species. New South Wales (NSW), in eastern Australia, has been identified as a region requiring improved information on foraging ecology and habitat use by green turtles. Aims The aim of this study was to use stable-isotope analyses to investigate diet composition and foraging ecology of green turtles found stranded along the NSW coastline from 2018 to 2021. Methods This study measured δ13C, δ15N, and δ34S in macrophyte (mangrove, seagrass, and algae) samples collected along the NSW coastline, between March and June 2021, and epidermis tissue from green turtles that stranded in the same region between 2018 and 2021. In addition, stable-isotope values for animals known, or expected, to be consumed by green turtles were sourced from the literature. Macrophyte stable-isotope values were mapped to display spatial variations, then combined with literature-sourced animal matter and measured epidermis isotope values into stable-isotope mixing models. Mixing models were used to determine diet structure for each stranded green turtle, and their similarity to regional macrophyte isotope values to infer potential foraging locations. Key results High variation was present in δ13C, δ15N, and δ34S values of macrophyte sources along the NSW coastline, limiting the potential to infer the recent foraging locations of stranded green turtles. High δ15N values in green turtle epidermis samples indicated that most sampled turtles were feeding two to three trophic levels above primary producers within algal-based food webs. Mixing models suggested that these food webs were predominantly supported by algae (mean ± s. d. = 51.2 ± 6.1%) and animal material (31.4 ± 4.7%), with mangrove (13.4 ± 2.0%) and seagrass (4.0 ± 2.5%) representing much smaller proportions of overall diet composition. Conclusions The results showed that green turtles stranded along the NSW coastline feed primarily in algae-dominated food webs, with evidence of omnivory. These findings suggest that sampled individuals display diet compositions alternative to those of their Queensland counterparts, who feed primarily in seagrass-dominated habitats. Management and conservation programs in NSW should focus on limiting anthropogenic disturbances in algae-dominated habitats. Implications This novel finding demonstrated the importance of algae-dominated habitats for green turtle conservation and management in south-eastern Australia. The generated isoscapes are useful in examining isotopic variations in macrophytes along the NSW coastline.
Lexical anticipation in bilinguals
Authors: Moreno Eva M. , Martin Clara D. , Foucart Alice
Published: December 2024

This chapter aims to acknowledge Prof. Albert
Costa’s contribution to the research field of language anticipation
in L2 readers/listeners. It starts with a brief introduction to
contrasting psycholinguistic models regarding the issue of lexical
pre-activation during language comprehension and it describes how
the Event Related Potential (ERP) technique advanced the
anticipation/integration debate in native (L1) speakers. Then, the
first studies looking at lexical anticipation in a second language
(L2) with ERPs conducted by Costa’s lab are reported. The following
section describes the influence of Costa’s results in the debate on
the pre-activation of the phonological form of predictable words, as
well as how his original work developed into further work on lexical
anticipation in L2 at sentence and discourse levels. Costa’s
heritage extended to other linguistic aspects related to L2, like
processing foreign-accented speech. The chapter ends with some
conclusions and future directions.
Discovery of the closest free-living relative of the domesticated “magic mushroom”Psilocybe cubensisin Africa
Authors: Bradshaw Alexander J , Sharp Cathy , Van Der Merwe Breyten , Tremble Keaton , Dentinger Bryn T.M.
Published: December 2024

The “magic mushroom”Psilocybe cubensisis cultivated worldwide for recreational and medicinal uses. Described initially from Cuba in 1904, there has been substantial debate about its origin and diversification. The prevailing view, first proposed by thePsilocybeexpert Gastón Guzmán in 1983, is thatP. cubensiswas inadvertently introduced to the Americas when cattle were introduced to the continents from Africa and Europe (∼1500 CE), but that its progenitor was endemic to Africa. This hypothesis has never been tested. Here, we report the discovery of the closest wild relative ofP. cubensisfrom sub-Saharan Africa,P. ochraceocentratanom. prov. Using DNA sequences from type specimens of all known and accessable African species ofPsilocybe, multi-locus phylogenetic and molecular clock analysis strongly support recognizing the African samples as a new species that last shared a common ancestor withP. cubensis∼1.5 million years ago (∼710k - 2.55M years ago 95% HPD). Even at the latest estimated time of divergence, this long predates cattle domestication and the origin of modern humans. Both species are associated with herbivore dung, suggesting this habit likely predisposedP. cubensisto its present specialization on domesticated cattle dung. Ecological niche modeling using bioclimatic variables for global records of these species indicates historical presence across Africa, Asia, and the Americas over the last 3 million years. This discovery sheds light on the wild origins of domesticatedP. cubensisand provides new genetic resources for research on psychedelic mushrooms.
Evolution of ivermectin resistance in the nematode modelCaenorhabditis elegans: critical influence of population size and unexpected cross-resistance to emodepside
Authors: Hellinga Jacqueline , Trubenova Barbora , Wagner Jessica , Regoes Roland R. , Krücken Jürgen , Schulenburg Hinrich , von Samson-Himmelstjerna Georg
Published: December 2024

The emergence and spread of anthelmintic resistance represent a major challenge for treating parasitic nematodes, threatening mass-drug control programs in humans and zoonotic species. Currently, experimental evidence to understand the influence of management (e.g., treatment intensity and frequency) and parasite-associated factors (e.g., genetic variation, population size and mutation rates) is lacking. To rectify this knowledge gap, we performed controlled evolution experiments with the model nematodeCaenorhabditis elegansand further evaluated the evolution dynamics with a computational model. Large population size was critical for rapid ivermectin resistance evolutionin vitroandin silico. Male nematodes were favored during resistance evolution, indicating a selective advantage of sexual recombination under drug pressurein vitro. Ivermectin resistance evolution led to the expected emergence of cross-resistance to the structurally related anthelmintic moxidectin but unexpectedly also to the structurally unrelated anthelmintic emodepside that has an entirely different mode of action. In contrast, albendazole, levamisole, and monepantel efficacy were not influenced by the evolution of Ivermectin resistance. We conclude that combining computational modeling within vitroevolution experiments to test specific aspects of evolution directly represents a promising approach to guide the development of novel treatment strategies to anticipate and mitigate resistance evolution in parasitic nematodes.
Genetic differentiation in theMAT-proximal region is not sufficient for suppressing recombination inPodospora anserina
Authors: Grognet Pierre , Debuchy Robert , Giraud Tatiana
Published: December 2024

Recombination is advantageous over the long-term, as it allows efficient selection and purging deleterious mutations. Nevertheless, recombination suppression has repeatedly evolved in sex chromosomes and mating-type chromosomes. The evolutionary causes for recombination suppression and the proximal mechanisms preventing crossing overs are still poorly understood. Several hypotheses have recently been suggested based on theoretical models, and in particular, that divergence could accumulate neutrally around a sex-determining region and reduce recombination rates, a self-reinforcing process that could foster progressive extension of recombination suppression. The ascomycete fungusPodospora anserinais an excellent model for investigating these questions. A 0.8 Mb region around the mating-type locus is non-recombining, despite being collinear between the two mating types. This fungus is mostly selfing, so that strains are highly homozygous, except in the non-recombining region around the mating-type locus that displays differentiation between mating types. Here, we generated a mutant to test the hypothesis that sequence divergence alone is responsible for recombination cessation. We replaced themat-idiomorph by the sequence of themat+idiomorph, to obtain a strain that is sexually compatible with themat-reference strain and isogenic to this strain in theMAT-proximal region. Crosses showed that recombination was still suppressed in theMAT-proximal region in the mutant strains, indicating that other proximal mechanisms than inversions or mere sequence divergence are responsible for recombination suppression in this fungus. This finding suggests that selective mechanisms likely acted for suppressing recombination, as the neutral model does not seem to hold, at least in this fungus.

ARTICLE SUMMARY

In many organisms, a non-recombining region is observed around the sex-determining locus. In the fungusPodospora anserina, recombination is suppressed within an 800kb region around the mating-type locus. In natural strains, the genome is isogenic between two mating-types, except in this region displaying heterozygosity. To determine if this heterozygosity can be responsible for the lack of recombination, compatible strains were engineered to be isogenic, including in the non-recombining region. Recombination inhibition persisted, indicating that mere sequence divergence does not cause recombination suppression. Our study provides an interesting insight on the molecular and evolutionary causes of recombination inhibition.
Coverage landscape of the human genome in nucleus DNA and cell-free DNA
Authors: Luo Jiaqi , Li Shuai Cheng
Published: December 2024

For long, genome-wide coverage has been used as a measure of sequencing quality and quantity, but the biology hidden beneath has not been fully exploited. Here we performed a comparative analysis on genome-wide coverage profiles between nucleus genome DNA (gDNA) samples from the 1000 Genomes Project (n=3,202) and cell-free DNA (cfDNA) samples from healthy controls (n=113) or cancer patients (n=362). Regardless of sample type, we observed an overall conserved landscape with segmentation of coverage, where adjacent windows of genome positions present similar coverage. Besides GC-content, we identified protein-coding gene density and nucleosome density as major factors influencing the coverage of gDNA and cfDNA, respectively. Differential coverage of cfDNA vs gDNA was found in immune-receptor loci, intergenic regions and non-coding genes, reflecting distinct genome activities in different cell types. A further rise in coverage at non-coding genes and intergenic regions plus a further drop of coverage at protein-coding genes and genic regions within cancer cfDNA samples indicated a loss of contribution by normal cells. Importantly, we observed the distinctive feature of coverage convergence in cancer-derived cfDNA, with the extent of convergence positively correlated to stages. Based on the findings, we developed and validated an outlier-detection approach for cfDNA-based cancer screening without the need of cancer samples for training, outperforming current benchmarks on condition-matched and condition-unmatched cancer detection tasks.
GraphVelo allows for accurate inference of multimodal velocities and molecular mechanisms for single cells
Authors: Chen Yuhao , Zhang Yan , Gan Jiaqi , Ni Ke , Chen Ming , Bahar Ivet , Xing Jianhua
Published: December 2024

RNA velocities and generalizations emerge as powerful approaches for extracting time-resolved information from high-throughput snapshot single-cell data. Yet, several inherent limitations restrict applying the approaches to genes not suitable for RNA velocity inference due to complex transcriptional dynamics, low expression, or lacking splicing dynamics, or data of non-transcriptomic modality. Here, we present GraphVelo, a graph-based machine learning procedure that uses as input the RNA velocities inferred from existing methods and infers velocity vectors lying in the tangent space of the low-dimensional manifold formed by the single cell data. GraphVelo preserves vector magnitude and direction information during transformations across different data representations. Tests on multiple synthetic and experimental scRNA-seq data including viral-host interactome and multi-omics datasets demonstrate that GraphVelo, together with downstream generalized dynamo analyses, extends RNA velocities to multi-modal data and reveals quantitative nonlinear regulation relations between genes, virus and host cells, and different layers of gene regulation.
An RNAi screen of Rab GTPase genes inC. elegansreveals that somatic cells of the reproductive system depend onrab-1for morphogenesis but not stem cell niche maintenance
Authors: Scott Kayt , Singh Noor , Gordon Kacy Lynn
Published: December 2024

Membrane trafficking is a crucial function of all cells and is regulated at multiple levels from vesicle formation, packaging, and localization to fusion, exocytosis, and endocytosis. Rab GTPase proteins are core regulators of eukaryotic membrane trafficking, but developmental roles of specific Rab GTPases are less well characterized, potentially because of their essentiality for basic cellular function.C. elegansgonad development entails the coordination of cell growth, proliferation, and migration—processes in which membrane trafficking is known to be required. Here we take an organ-focused approach to Rab GTPase functionin vivoto assess the roles of Rab genes in reproductive system development. We performed a whole-body RNAi screen of the entire Rab family inC. elegansto uncover Rabs essential for gonad development. Notable gonad defects resulted from RNAi knockdown ofrab-1,the key regulator of ER-Golgi trafficking. We then examined the effects of tissue-specific RNAi knockdown ofrab-1in somatic reproductive system and germline cells. We interrogated the dual functions of the distal tip cell (DTC) as both a leader cell of gonad organogenesis and the germline stem cell niche. We find thatrab-1functions cell-autonomously and non-cell-autonomously to regulate both somatic gonad and germline development. Gonad migration, elongation, and gamete differentiation—but surprisingly not germline stem niche function—are highly sensitive torab-1RNAi.

The Rab family of GTPases regulate vesicular trafficking in cells. This study assessed the consequences for the growth of the gonad of RNAi-mediated gene knockdown of all Rab GTPase genes inC. elegans. The highly conserved primary regulator of ER-Golgi trafficking,rab-1, is essential for normal gonad and germline development. Further experiments found thatrab-1is required in the somatic gonad for gonad elongation and migration, germline proliferation, and proper gamete formation. Surprisingly, the ability of the germline stem cell niche to maintain germ cells in the proliferative stem-like state was not affected byrab-1RNAi knockdown.
Dietary intervention in captive-bred hares fails to enrich gut microbiomes with wild-like functions
Authors: Aizpurua Ostaizka , Martin-Bideguren Garazi , Gaun Nanna , Alberdi Antton
Published: December 2024

Reintroducing captive-bred animals into the wild often faces limited success, with the underlying causes frequently unclear. One emerging hypothesis is that maladapted gut microbiota may play a significant role in these challenges. To investigate this possibility, we employed genome-resolved metagenomics to analyse the taxonomic and functional differences in the gut microbiota of wild and captive European hares (Lepus europaeus), as well as to assess the impact of a dietary switch to grass aimed at pre-adapting captive hares to wild conditions. Our analyses recovered 860 metagenome-assembled genomes, with 87% of them representing novel species. We found significant taxonomic and functional differences between the gut microbiota of wild and captive hares, notably the absence of Spirochaetota in captive animals and differences in amino acid and sugar degradation capacities. While the dietary switch to grass induced some minor changes in the gut microbiota, it did not result in a shift towards a more wild-like microbial community. The increased capacity for degrading amino acids and specific sugars observed in wild hares suggest that, instead of bulk grass, dietary interventions tailored to their specific dietary preferences might be necessary for pre-adapting hare gut microbiota to wild conditions.

Importance

This study sheds light on the critical role of gut microbiota in the success of reintroducing captive-bred animals into the wild. By comparing the gut microbiota of wild and captive European hares, we identified significant taxonomic and functional differences, including the absence of key microbial groups in captive hares. Dietary interventions, such as switching to grass, showed limited success in restoring a wild-like microbiota, highlighting the need for tailored approaches to mimic natural diets. With 87% of recovered microbial genomes representing novel species, this research also enriches our understanding of microbial diversity in wildlife. These findings emphasise that maladapted gut microbiota may hinder the survival and adaptation of reintroduced animals, suggesting that microbiome-targeted strategies could improve conservation efforts and the success of animal rewilding programs.
Identification of an Outbreak of Bivalve Transmissible Neoplasia in Soft-Shell Clams (Mya arenaria) in the Puget Sound Using Hemolymph and eDNA Surveys
Authors: Weinandt Sydney A. , Child Zachary J. , Lartey Dorothy , Santos Angel , Maxfield Holden , Sevigny Jordana K. , Garrett Fiona E. S. , Smith Peter D. , Giersch Rachael M. , Hart Samuel F. M. , Perez Franchesca , Rabins Lucas , Kaiser Samuel , Boyar Anna , Newton Jan , Kerr Jesse , Dimond James L. , Metzger Michael J.
Published: December 2024

Bivalve transmissible neoplasia (BTN) is one of three known types of naturally transmissible cancer— cancers in which the whole cancer cells move from individual to individual, spreading through natural populations. BTN is a lethal leukemia-like cancer that has been observed throughout soft-shell clam (Mya arenaria) populations on the east coast of North America, with two distinct sublineages circulating at low enzootic levels in New England, USA, and Prince Edward Island, Canada. Major cancer outbreaks likely due toMya arenariaBTN (MarBTN) were reported in 1980s and the 2000s and the disease has been observed since the 1970s, but it has not been observed in populations of this clam species on the US west coast. In 2022, we collected soft-shell clams from several sites in Puget Sound, Washington, USA, and unexpectedly found high prevalence of BTN in two sites (Triangle Cove on Camano Island and near Stanwood in South Skagit Bay). Prevalence of BTN increased in subsequent years, reaching >75% in both sites in 2024, while it was not observed in other sites, suggesting the early stages of a severe disease outbreak following recent introduction. We observed that these cancer cells contain several somatic transposing insertion sites found only in the USA-sublineage of MarBTN, showing that it likely was recently transplanted from New England to this location. We then developed a sensitive environmental DNA (eDNA) assay, using qPCR to target somatic mutations in the MarBTN mitogenome, and showed that MarBTN can be detected in seawater at Triangle Cove, as well as several kilometers outside of the cove. We then used this assay to survey 50 sites throughout Puget Sound, confirming that the disease can be detected at high levels at Triangle Cove and South Skagit Bay, and showing that it extends beyond these known sites. However, while normal soft-shell clam mtDNA was widely detected, MarBTN was undetectable throughout most of Puget Sound and currently remains limited to the South Skagit Bay area and north Port Susan. These results identify a previously unknown severe outbreak of a transmissible cancer due to long-distance transplantation of disease from another ocean, and they demonstrate the utility of eDNA methods to track the spread of BTN through the environment.
A ML Framework for Genetic Sequence Identification using 2D Electrical Conductance Probability Distributions from Mixed Data Sets
Authors: Wang Yiren , Wang Hongning , Das Arindam K. , Anantram M. P.
Published: December 2024

Genetic sequence identification from electrical characterization of single molecules has emerged as a promising alternative to traditional approaches. Since electrical data on single molecules is extremely noisy due to the limitations of even state-of-the-art approaches, achieving high detection rates is challenging, particularly when the task involves being able to distinguish a sequence from its single base-pair mismatches. To address this issue, we propose an architecture based on combining a convolutional neural network with an ensemble learning method, XGBoost. In addition, four different input feature representations are considered, 1D conductance probability distributions and 2D conductance versus distance probability distributions which can be viewed as images, with or without averaging over the experimental parameters. The with averaging case corresponds to feature matrices derived from mixed datasets. We find that 2D probability distributions are helpful with respect to classifier accuracy, but averaged conductance probability distributions are much more impactful and significantly enhance prediction accuracy. Our quantitative analysis of multiple sequences shows an impressive performance increase of approximately 10% for all sequences. While the basis of our analysis is conductance data of DNA strands for COVID-19 Alpha, Beta, and Delta variants and their single base-pair mismatches, our method is generally applicable to other single-molecule identification based on their conductance.
A model of inborn metabolism errors associated with adenine amyloid-like fiber formation reduces TDP-43 aggregation and toxicity in yeast
Authors: Park Sangeun , Park Sei-Kyoung , Liebman Susan W.
Published: December 2024

TDP-43 is linked to human diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). Expression of TDP-43 in yeast is known to be toxic, cause cells to elongate, form liquid-like aggregates, and inhibit autophagy and TOROID formation. Here, we used theapt1Δ aah1Δyeast model of disorders of inborn errors of metabolism, previously shown to lead to intracellular adenine accumulation and adenine amyloid-like fiber formation, to explore interactions with TDP-43. Results show that the double deletion shifts the TDP-43 aggregates from a liquid-like, toward a more amyloid-like, state. At the same time the deletions reduce TDP-43’s effects on toxicity, cell morphology, autophagy, and TOROID formation without affecting the level of TDP-43. This suggests that the liquid-like and not amyloid-like TDP-43 aggregates are responsible for the deleterious effects in yeast. How theapt1Δ aah1Δdeletions alter TDP-43 aggregate formation is not clear. Possibly, it results from adenine/TDP-43 fiber interactions as seen for other heterologous fibers. The work offers new insights into the potential interactions between metabolite-based amyloids and pathological protein aggregates, with broad implications for understanding protein misfolding diseases.
Serum lipid reference intervals of high-density and low-density lipoprotein cholesterols and their association with atherosclerosis and other factors in Psittaciformes
Authors: Janeczek Matthias , Korbel Rüdiger , Janeczek Friedrich , Alber Helen , Küchenhoff Helmut , Rinder Monika
Published: December 2024

The prevalence of atherosclerosis is high in captive psittacine populations and the disease and subsequent heart problems have become a common reason for consultations in avian veterinary practices. To this day, ante-mortem diagnosis in birds remains challenging, however the serum lipoprotein-panel has been suggested to potentially aid in the diagnosis of the disease and provide better understanding of the pathogenesis. In parrots, unlike in humans, an association between serum lipoproteins and atherosclerosis has not been proven so far. The present retrospective cohort study aimed to establish multi-genera serum reference intervals for high-density-lipoprotein cholesterol (HDL-C) and low-density-lipoprotein cholesterol (LDL-C) in various parrot species. In addition, an evaluation on the changes of HDL-C and LDL-C depending on intrinsic and extrinsic factors of genus, age, sex, diet, prevalence of atherosclerosis, reproductive activity and body condition score was performed. An analysis of 1199 blood samples originating from 694 birds of multiple parrot genera revealed genus-specific variations in lipoprotein levels. Lipoproteins were studied for their association with independent variables of diet, age, sex, reproductive and breeding status, atherosclerosis and body conditioning score. A significant association between LDL-C levels and the prevalence of atherosclerosis could be observed, similar to findings in humans. Diet was found to be influencing both lipoprotein levels and risk for the development of atherosclerotic disease. Results showed, that LDL-C appears to be a potential predictor of atherosclerosis, while the role of HDL-C remained less conclusively defined. The results of the study provide a foundational framework for the future use of lipoprotein analysis in parrot medicine, offering novel insights into the management of cardiovascular health in pet parrots.
The complex development of psoralen-interstrand crosslink resistance inEscherichia colirequires AcrR inactivation, retention of amarboxsequence, and one of three MarA, SoxS, or Rob global regulators
Authors: Worley Travis K , Asal Ayah H , Cooper Lo , Courcelle Charmain T , Courcelle Justin
Published: December 2024

Crosslinking agents, such as psoralen and UVA radiation, can be effectively used as antimicrobials and for treating several dysplastic conditions in humans, including some cancers. Yet, both cancer cells and bacteria can become resistant to these compounds, making it important to understand how resistance develops. Recently, several mutants were isolated that developed high-levels of resistance to these compounds through upregulation of components of the AcrAB-TolC-efflux pump. Here, we characterized these mutants and found that resistance specifically requires inactivating mutations of theacrRtranscriptional repressor which also retain themarboxsequence found within this coding region. In addition, the presence of any one of three global regulators, MarA, SoxS, or Rob, is necessary and sufficient to bind to themarboxsequence and activate resistance. Notably, although psoralen is a substrate for the efflux pump, these regulators are not naturally responsive to this stress as neither psoralen, UVA, nor crosslink induction upregulatesacrABexpression in the absence of mutation.

Highlights

Psoralen crosslink resistance requires AcrR inactivation and MarA/SoxS/Rob activation

Psoralen crosslink resistance is mediated by upregulating the AcrAB-TolC efflux pump

AcrAB-TolC can utilize psoralen as a substrate but not upregulated by this stress

Acquiring resistance to DNA interstrand crosslinks requires mutation
Structural regeneration and functional recovery of the olfactory system of zebrafish following brain injury
Authors: Calvo-Ochoa Erika , Vorhees Nathaniel W. , Lockett Theodore P. , DeWitt Skylar L. , Thomas Evan A. , Gray Abigail B. , Miyasaka Nobuhiko , Yoshihara Yoshihiro , Byrd-Jacobs Christine A.
Published: December 2024

Olfactory dysfunction is a common outcome of brain injuries, negatively affecting quality of life. The mammalian nervous system has limited capacity for spontaneous olfactory recovery, making it challenging to study olfactory regeneration and recovery in adults. In contrast, zebrafish are an ideal model for such studies due to its extensive and lifelong regenerative abilities. In this work, we describe a model of excitotoxic injury in the olfactory bulb using quinolinic acid (QA) lesions in adult zebrafish. We observed extensive neurodegeneration in both the olfactory bulb and olfactory epithelium, including a reduction of bulbar volume, neuronal death, and impaired olfactory function. Recovery mechanisms involved tissue remodeling, cell proliferation, neurogenesis, leading to full restoration of olfactory function by 21 days. This study provides a model to further investigate the effects of excitotoxicity on olfactory dysfunction, and highlights the remarkable regenerative abilities of zebrafish, providing insights into potential therapeutic strategies for restoring olfactory function following brain injuries.
CAFE: An Integrated Web App for High-Dimensional Analysis and Visualization in Spectral Flow Cytometry
Authors: Siam Md Hasanul Banna , Ali Md Akkas , Vardaman Donald , Acharyya Satwik , Patil Mallikarjun , Tyrrell Daniel J.
Published: December 2024

Spectral flow cytometry provides greater insights into cellular heterogeneity by simultaneous measurement of up to 50 markers. However, analyzing such high-dimensional (HD) data is complex through traditional manual gating strategy. To address this gap, we developed CAFE as an open-source Python-based web application with a graphical user interface. Built with Streamlit, CAFE incorporates libraries such as Scanpy for single-cell analysis, Pandas and PyArrow for efficient data handling, and Matplotlib, Seaborn, Plotly for creating customizable figures. Its robust toolset includes density-based down-sampling, dimensionality reduction, batch correction, Leiden-based clustering, cluster merging and annotation. Using CAFE, we demonstrated analysis of a human PBMC dataset of 350,000 cells identifying 16 distinct cell clusters. CAFE can generate publication-ready figures in real time via interactive slider controls and dropdown menus, eliminating the need for coding expertise and making HD data analysis accessible to all. CAFE is licensed under MIT and is freely available athttps://github.com/mhbsiam/cafe.
TurboID-based proximity labeling identifies novel germline proteins that maintain E granule integrity and small RNA homeostasis inC. elegans
Authors: Li Kun , Feng Xuezhu , Wang Ke , Huang Xiaona , Zhu Chengming , Huang Xinya , Wen Quan , Guang Shouhong , Chen Xiangyang
Published: December 2024

Germ granules are biomolecular condensates composed of RNA and proteins that play crucial roles in RNA metabolism and posttranscriptional gene regulation.C. elegansgerm granules consist of at least seven distinct subcompartments, including P granules, Z granules, Mutator foci, SIMR foci, P-bodies, D granules and E granules. Among these condensates, the E granule, which is nonrandomly positioned within the germ granule, is required for the production of a specialized class of small interfering RNAs (siRNAs). However, the mechanisms underlying E granule formation and its functional significance remain largely unexplored. In this study, via the use of TurboID- based proximity labeling technology combined with an RNAi-based reverse genetic screen, we identified two novel components of the E granule, EGC-2/C27B7.5 and EGC-3/F59G1.8, which initiate E granule assembly. The depletion of EGC-2 or EGC- 3 disrupts the perinuclear localization of the EGO and PICS complexes, both of which are enriched in E granules and are required for E-class siRNA and piRNA biogenesis, respectively. Small RNAomic analyses revealed that both EGC-2 and EGC-3 promote the production of 5’E-class siRNA, whereas prohibiting piRNA maturation. Taken together, our results elucidate the roles of EGC-2 and EGC-3 in maintaining E granule integrity and small RNA homeostasis, and suggest that intracellular condensation may exert distinct regulatory effects on different biological processes. Additionally, the combination of proximity labeling technology and reverse genetic screening provides a robust strategy for studying the assembly of biomolecular condensates.
A neural circuit for context-dependent multimodal signaling inDrosophila
Authors: Steinfath Elsa , Khalili Afshin , Stenger Melanie , Schultze Bjarne L. , Ravindran Sarath Nair , Alizadeh Kimia , Clemens Jan
Published: December 2024

Many animals, including humans, produce multimodal displays by combining acoustic with visual or vibratory signals [1–4]. However, the neural circuits that coordinate the production of multiple signals in a context-dependent manner are unknown. Multimodal behaviors could be produced by parallel circuits that independently integrate the external cues that trigger each signal. We find that multimodal signals inDrosophilaare driven by a single circuit that integrates external sensory cues with internal motivational state and circuit dynamics.Drosophilamales produce air-borne song and substrate-borne vibration during courtship and previous studies have identified neurons that drive courtship and singing, but the contexts and circuits that drive vibrations and coordinate multimodal signaling were not known [5–11]. We show that males produce song and vibration in distinct, largely non-overlapping contexts and that brain neurons that drive song also drive vibrations with cell-type specific dynamics and via separate pre-motor pathways. This circuit also coordinates multimodal signaling with ongoing behavior, namely locomotion, to drive vibrations only when the male’s vibrations can reach the female. A shared circuit facilitates the control of signal dynamics by external cues and motivational state through shared mechanisms like recurrence and mutual inhibition. A proof-of-concept circuit model shows that these motifs are sufficient to explain the behavioral dynamics. Our work shows how simple motifs can be combined in a single neural circuit to select and coordinate multiple behaviors.
Estimating survival of an anadromous salmonid using Bayesian hierarchical models applied to acoustic telemetry, biological, and environmental data
Authors: Munaweera Inesh , Harris Les N. , Moore Jean-Sébastien , Tallman Ross F. , Gilbert Matthew J.H. , Fisk Aaron T. , Else Brent G. T. , Ahmed Mohamed M. M. , Gillis Darren M. , Muthukumarana Saman
Published: December 2024

Hierarchical modelling is frequently used to model ecological processes because of its ability to handle complex ecological phenomena by decomposing them into naturally explainable sub-models. Hierarchical Bayesian approaches have gained widespread use in health, social, and environmental sciences, including in the estimation of demo-graphic parameters such as survival. In this study, we combine Bayesian hierarchical models with acoustic telemetry data to estimate survival probabilities for high-latitude populations of an anadromous salmonid, the Arctic char(Salvelinus alpinus), while in-corporating environmental and biological covariates to assess their impact on survival. The model we present here can also account for temporally varying detection probabilities due to changes to the acoustic receiver array design and seasonal variation in the detection probabilities related to environmental conditions (e.g., ice vs. no ice). As previously documented in this species, survival was high (>0.87) and we found that the covariates pertaining to sea ice coverage and Fulton’s condition factor impacted the survival probabilities. Contrary to our expectations, high-condition fish had lower survival rates. Survival was also considerably lower during the summer (open-water) compared to winter (ice-covered) seasons. While the biological explanations and implications of these findings require further exploration, they nonetheless demonstrate the utility of this approach. Specifically, we present a hierarchical Bayesian model that can consider environmental and biological covariates while accounting for varying detection probabilities, a major concern of acoustic telemetry studies. The model can be easily adapted for other taxa with similar life histories where mark recapture data are available and can be extended to include additional environmental (e.g., salinity) and biological parameters (e.g., sex).