bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-Related Cerebral Ventriculomegaly occurs in Patients with Primary Ciliary Dyskinesia
Authors: Eisenhuth Franziska , Agbonze Joy E. , Groh Adam M.R. , Rudko David A. , Stratton Jo Anne , Shapiro Adam J. 
Published: August 2024

AbstractPrimary ciliary dyskinesia (PCD) is a genetic disorder causing motile ciliary dysfunction primarily affecting the respiratory and reproductive systems. However, the impact of PCD on the central nervous system, through dysfunction of motile cilia in multiciliated ependymal cells, remains poorly understood. We hypothesized that patients with PCD exhibit sub-clinical ventriculomegaly due to ependymal ciliary dysfunction, which may influence neuropsychiatric diagnoses.We demonstrated highly specific expression levels of known PCD-related genes in human brain ependymal cells (p<0.0001), supporting their potential role in regulating ependymal ciliary function. Computed tomography sinus images from patients with PCD (n=33) and age/sex-matched controls (n=64) were analysed. Patients with PCD displayed significantly larger ventricular areas (p<0.0001) and Evans index (p<0.01), indicating ventriculomegaly that was consistent across all genetic subgroups. Ventricular enlargement correlated positively with increasing age in patients with PCD compared to controls (p<0.001). Chart review demonstrated a high prevalence (39%) of neuropsychiatric/neurological disorders in adult PCD patients that did not correlate with degree of ventriculomegaly.Our findings suggest that patients with PCD may have unrecognized, mild ventriculomegaly potentially due to ependymal ciliary dysfunction which correlates with ageing. Further study is required to determine if ventricular enlargement contributes to neuropsychiatric/neurological or other morbidity in PCD.
EMhub: a web platform for data management and on-the-fly processing in scientific facilities
Authors: De la Rosa-Trevin Jose M. , Sharov Grigory , Fleischmann Stefan , Morado Dustin , Bollinger John C. , Miller Darcie J. , Terry Daniel S. , Blanchard Scott C. , Fernandez Israel S. , Carroni Marta 
Published: August 2024

AbstractMost scientific facilities produce large amounts of heterogeneous data at a rapid pace. Managing users, instruments, reports, and invoices presents additional challenges. To address these challenges, we introduce EMhub, a web platform designed to support the daily operations and record-keeping of a scientific facility. EMhub enables easy management of user information, instruments, bookings, and projects. The application was initially developed to meet the needs of a CryoEM facility, but its functionality and adaptability have proven broad enough to be extended to other data-generating centers. The expansion of EMHub is enabled by the modular nature of its core functionalities. The application allows external processes to be connected via a REST API, automating tasks such as folder creation, user and password generation, and execution of real-time data processing pipelines. EMhub has been used for several years at the Swedish National CryoEM Facility and installed in the CryoEM center at the Structural Biology Department at St. Jude Children’s Research Hospital. A fully automated single-particle pipeline has been implemented for on-the-fly data processing and analysis. At St. Jude, the X-Ray Crystallography Center and the Single-Molecule Imaging Center have already expanded the platform to support their operational and data management workflows.
Under Cover of Darkness: Refuge from Artificial Light at Night may Mitigate Risks to Stranded Seabirds
Authors: Brown Taylor M. , Baker Kaitlyn , Wilhelm Sabina I. , Burness Gary 
Published: August 2024

ABSTRACTArtificial light at night is an anthropogenic pollutant that has wide-ranging effects on wildlife. Fledgling seabirds of the order Procellariiformes exhibit phototaxis toward artificial lights on their first flights from the nest, causing them to become grounded in human settlements where they are subject to increased risk of predation. Limited evidence suggests that certain light types may be less attractive than others, yet there is also evidence for an aversion to light under certain circumstances. We investigated differences in phototactic behaviour, activity level, and shelter-seeking behaviour of groundedHydrobates leucorhous(Leach’s storm-petrel) fledglings exposed to artificial light in three experiments: a Y-maze choice experiment, an open field test, and a modified open field test with a hide box provided (“Safe Haven test”). When provided with combinations of different light types in the Y-maze, storm-petrels typically remained stationary in the darkest part of the apparatus and exhibited no response toward one light type over another. This was consistent with results from the open field test, in which individuals were less active in darkness than when exposed to two out of three light conditions (Warm White Light-Emitting Diode and High Pressure Sodium). More than half of birds entered the hide box in light conditions, compared to none in the dark. Considered together, our results indicate Leach’s storm-petrel fledglings exhibit photophobic behaviour after stranding, which may be part of a behavioural strategy to avoid predation. Further, we demonstrate the utility of providing hide boxes to protect stranded seabird fledglings in locations where lighting cannot be eliminated or where rescue efforts may be limited in spatial or temporal coverage. However, hide boxes would have limited utility in dark locations. Hide boxes constitute a novel mitigation measure that merits future testing for its ability to reduce stranding-induced mortality, especially in imperiled procellariiform species.LAY SUMMARYGlobally, fledglings of many seabird species become stranded in towns and at industrial sites near their breeding coloniesStrandings are thought to be caused by attraction to lights, although some species appear to avoid lightWe tested behavioural responses and activity levels of Leach’s storm-petrel fledglings toward several different light typesWhen presented with different types of light in a choice experiment, most birds remained stationaryFledglings were more active in warm-hued lights than in darknessBirds sought shelter when it was provided in light conditions, but not when provided in darknessOur results suggest that rescue programs targeting Leach’s storm-petrels should include searches in dark, hidden locations where fledglings are likely to hide, and support the use of small shelters to protect stranded seabirds when lights cannot be turned off
DNA damage-associated protein co-expression network in cardiomyocytes informs on tolerance to genetic variation and disease
Authors: Johnson Omar D. , Paul Sayan , Gutierrez Jose A. , Russell William K. , Ward Michelle C. 
Published: August 2024

SummaryCardiovascular disease (CVD) is associated with both genetic variants and environmental factors. One unifying consequence of the molecular risk factors in CVD is DNA damage, which must be repaired by DNA damage response proteins. However, the impact of DNA damage on global cardiomyocyte protein abundance, and its relationship to CVD risk remains unclear. We therefore treated induced pluripotent stem cell-derived cardiomyocytes with the DNA-damaging agent Doxorubicin (DOX) and a vehicle control, and identified 4,178 proteins that contribute to a network comprising 12 co-expressed modules and 403 hub proteins with high intramodular connectivity. Five modules correlate with DOX and represent distinct biological processes including RNA processing, chromatin regulation and metabolism. DOX-correlated hub proteins are depleted for proteins that vary in expression across individuals due to genetic variation but are enriched for proteins encoded by loss-of-function intolerant genes. While proteins associated with genetic risk for CVD, such as arrhythmia are enriched in specific DOX-correlated modules, DOX-correlated hub proteins are not enriched for known CVD risk proteins. Instead, they are enriched among proteins that physically interact with CVD risk proteins. Our data demonstrate that DNA damage in cardiomyocytes induces diverse effects on biological processes through protein co-expression modules that are relevant for CVD, and that the level of protein connectivity in DNA damage-associated modules influences the tolerance to genetic variation.
New viruses infecting hyperthermophilic bacteriumThermus thermophilus
Authors: Kolesnik Matvey , Pavlov Constantine , Demkina Alina , Samolygo Aleksei , Karneyeva Karyna , Trofimova Anna , Sokolova Olga S. , Moiseenko Andrei V. , Kirsanova Maria , Severinov Konstantin 
Published: August 2024

AbstractHighly diverse phages infecting thermophilic bacteria of theThermusgenus have been isolated over the years from hot springs around the world. Many of these phages are unique, rely on highly unusual developmental strategies, and encode novel enzymes. The variety ofThermusphages is clearly undersampled, as evidenced, for example, by a paucity of phage-matching spacers inThermusCRISPR arrays. Using water samples collected from hot springs in the Kunashir Island from the Kuril archipelago and from the Tsaishi and Nokalakevi districts in the Republic of Georgia we isolated several distinct phages infecting laboratory strains ofThermus thermophilus. Genomic sequence analysis of 11 phages revealed both close relatives of previously describedThermusphages isolated from geographically distant sites, as well as phages with very limited similarity to earlier isolates. Comparative analysis allowed us to predict several accessory phage genes whose products may be involved in host defense/interviral warfare, including a putative Type V CRISPR-cassystem.
An ecological, phenotypic and genomic survey of duckweeds with their associated aquatic environments in the United Kingdom
Authors: Smith Kellie E. , Cowan Laura , Flis Paulina , Moore Chris , Heatley Matthew , Robles-Zazueta Carlos A. , Lee Adam , Yant Levi 
Published: August 2024

AbstractThe duckweeds feature global distributions and diverse applications in phytoremediation and nutrition, as well as use in fundamental studies of development. Existing collections have minimal environmental data linked to natural habitats. Thus, there is a lack of understanding of natural variation in the context of native habitats. Here, a novel collection of 124 duckweed accessions from 115 sites across the United Kingdom were characterised by genome sequencing and ionomics. In nutrient-replete conditions all accessions hyperaccumulated P, K, Mg and Ca. Local but not large-scale associations were revealed between elemental composition of duckweed in common, replete conditions and native water profiles.Lemna minorwas the most prevalent species in the UK, with a closely related hybridL. japonicafrequently found in waters with higher micronutrient concentrations. InvasiveL. minutawas common in the southern and midland regions, but restricted in Scotland.Lemnaaccessions accumulated heavy metal contaminants typically together with macronutrients, suggesting phytoremediation potential, but some limitations as food. Furthermore, monitoring the ecological interactions between native, hybrid and invasiveLemnaspecies should be ongoing in the interest of biodiversity.
Unveiling Mechanistic and Structural Insights of EstS1 Esterase: A Potent Broad-Spectrum Phthalate Diester Degrading Enzyme
Authors: Verma Shalja , Choudhary Shweta , Kumar K Amith , Mahto Jai Krishna , Vamsi K Anil Kumar , Mishra Ishani , Prakash Vellanki Bhanu , Sircar Debabrata , Tomar Shailly , Sharma Ashwani Kumar , Singla Jitin , Kumar Pravindra 
Published: August 2024

AbstractThe ubiquitous presence of plastics and plasticizers around the globe has raised an alarming condition. Phthalate diesters are high-priority pollutants that mimic natural hormones and act as endocrine disruptors upon entering living systems. While certain bacterial esterases have been identified for their role in phthalate diester degradation, their structural and mechanistic characteristics remain largely unexplored. A thermostable and pH-tolerant EstS1 esterase fromSulfobacillus acidophiluscatalyzes the conversion of low molecular weight phthalate diesters to monoesters. This study highlights the unique potential of EstS1 to degrade high molecular weight bis(2-ethylhexyl) phthalate (DEHP) by employing biophysical and biochemical approaches along with in-depth structural analysis utilizing high-resolution crystal structures in both apo and complex forms, with various substrates, products, and their analogs to elucidate mechanistic details. The catalytic tunnel mediating entry and exit of the substrate and product, respectively, centralized the Ser-His-Asp triad performing catalysis by bi-bi ping-pong mechanism, forming a tetrahedral intermediate. Additionally, structural analysis of the polypropylene analog jeffamine with EstS1 revealed effective covalent binding, demonstrating its multifunctional capability. Mutation analysis showed that the Met207Ala mutation abolished DEHP binding at the active site, confirming its essential role in supporting catalysis. These findings underscore the potential of EstS1 as a key tool for advancing technologies aimed at phthalate diesters biodegradation.
Territoriality and resource availability modulate the effect of conspecific encounters on the foraging behaviours of a mammalian predator
Authors: Clermont Jeanne , Dulude-de Broin Frédéric , Poulin Marie-Pier , Berteaux Dominique 
Published: August 2024

AbstractThe probability of encountering conspecifics shapes multiple dimensions of animal behaviour. For example, territorial individuals increase vigilance, scent marking and alarm calling when approaching home range boundaries. Whether territorial predators modify their foraging behaviours with respect to the probability of encountering neighbouring territory owners is poorly understood. However, this could strongly influence the landscape of predation risk and therefore modulate predator-prey interactions. We studied the movements and behaviours of 23 resident Arctic foxes occupying neighbouring home ranges during two years of contrasting resource availability (abundant resources in 2019, scarce resources in 2022) on Bylot Island, Nunavut, Canada. First, based on simultaneous GPS tracking of individuals, we established which individuals used a territory (an exclusive area) by estimating the spatial distribution of the probability of encountering a neighbour within their home range. Second, using GPS and accelerometry data, we evaluated if the probability of encountering a neighbour influenced the spatial distribution of foraging behaviours, and whether this relationship differed between territorial and non-territorial individuals. When resources were abundant, only breeding individuals excluded other foxes from a part of their home range and were thus territorial. When resources were rare, none of the foxes reproduced and all but one were territorial. Non-territorial individuals in 2019 were less likely to cache prey in areas with a high probability of encounter, possibly reducing the risk of cache pilfering. We found no effect of the probability of encounter on the behaviours of the non-territorial individual in 2022. The probability to cache prey of territorial individuals however did not depend on the probability of encountering a neighbour, suggesting they have no benefit of modulating the distribution of their caches according to potential encounters in a partly exclusive area. Our results thus suggest that Arctic foxes use different tactics to secure resources based on their degree of territoriality and the availability of resources. We highlight how the presence of resident, but non-territorial predators, whose home ranges overlap those of their territorial neighbours, may influence the distribution of predation risk by creating zones where predator density is high, potentially influencing predator-prey interactions.
Evolutionary Origins and Functional Diversification of Auxin Response Factors
Authors: Hernández-García Jorge , Carrillo-Carrasco Vanessa Polet , Rienstra Juriaan , Tanaka Keita , de Roij Martijn , Dipp-Álvarez Melissa , Freire-Ríos Alejandra , Crespo Isidro , Boer D. Roeland , van den Berg Willy A.M. , Lindhoud Simon , Weijers Dolf 
Published: August 2024

AbstractThe Auxin Response Factors (ARFs) family of transcription factors are the central mediators of auxin-triggered transcriptional regulation. Functionally different classes of extant ARFs operate as antagonistic auxin-dependent and -independent regulators. While part of the evolutionary trajectory to the present auxin response functions has been reconstructed, it is unclear how ARFs emerged, and how early diversification led to functionally different proteins. Here, we usein silicoandin vivoanalyses to revisit the molecular events that led to the origin and subsequent evolution of the ARFs. We reveal the shared origin of ARFs from preexisting domains, uncovering a protein fold homologous to the ARF DNA-binding fold in a conserved eukaryotic chromatin regulator. Building on this, we reconstruct the complete evolutionary history of ARFs, including the divergence events leading to the appearance of the ARF classes and defining the main molecular targets for their functional diversification. We derive a complete evolutionary trajectory that led to the emergence of the nuclear auxin signalling pathway.
Protein Carrier AAV
Authors: Hoffmann Mareike D. , Sorensen Ryan J. , Extross Ajay , He Yungui , Schmidt Daniel 
Published: August 2024

ABSTRACTAAV is widely used for efficient delivery of DNA payloads. The extent to which the AAV capsid can be used to deliver a protein payload is unexplored. Here, we report engineered AAV capsids that directly package proteins – Protein Carrier AAV (pcAAV). Nanobodies inserted into the interior of the capsid mediate packaging of a cognate protein, including Green Fluorescent Protein (GFP),Streptococcus pyogenesCas9, Cre recombinase, and the engineered peroxidase APEX2. We show that protein packaging efficiency is affected by the nanobody insertion position, the capsid protein isoform into which the nanobody is inserted, and the subcellular localization of the packaged protein during recombinant AAV capsid production; each of these factors can be rationally engineered to optimize protein packaging efficiency. We demonstrate that proteins packaged within pcAAV retain their enzymatic activity and that pcAAV can bind and enter the cell to deliver the protein payload. Establishing pcAAV as a protein delivery platform may expand the utility of AAV as a therapeutic and research tool.
NOK promotes tumorigenesis through coordinating epidermal growth factor receptor to boost the downstream signaling in breast cancer
Authors: Wang Yinyin , Zhang Bingdong , He Chunhua , Tian Bo , Liu Sihan , Li Jianghua , Wang Jiayu , Yang Shigao , Zhu Bingtao , Wang Xiaoguang , Chang Zhijie , Cao Chenxi 
Published: August 2024

AbstractBACKGROUNDEpidermal growth factor receptor (EGFR) forms a homodimer or heterodimer with other ErbB receptor family members to activate different downstream cytoplasmic signaling proteins during tumorigenesis.METHODSAdenovirus and lentivirus were used to overexpress or deplete NOK and/or EGFR to evaluate the phosphorylation of EGFR, the interaction of NOK-EGFR and their role in cell proliferation and metastasis.RESULTSEGFR heterodimerizes with NOK (also known as STYK1), a novel tyrosine kinase with a transmembrane domain, to promote tumorigenesis and metastasis of breast cancer cells. We found that NOK directly interacted with EGFR and formed a heterodimer complex. Depletion of NOK impaired, but over-expression of NOK increased, the phosphorylation of EGFR. NOK enhanced EGF signaling activation, in particular, the phosphorylation of STAT3, STAT5 and Erk1/2 via its juxtamembrane (JM) domain in promoting the proliferation and migration of breast cancer cells. Overexpression of NOK and EGFR synergistically induced the tumorigenesis of NIH-3T3 normal cells. We finally demonstrated that co-expression of NOK and EGFR correlated with tumor malignant stages in breast cancer patients.CONCLUSIONSOur findings uncover a mechanism by which NOK coordinates EGFR to enhance EGF signaling during tumorigenesis and metastasis and propose a potential strategy for targeting NOK-EGFR in breast cancer treatment.GRAPHICAL ABSTRACTEGFR heterodimerizes with NOK/STYK1, a novel tyrosine kinase with a transmembrane domain, in a manner of cross interaction via their juxtamembrane (JM) domains and kinase domains.NOK enhances EGF signaling activation, in particular, the phosphorylation of STAT3, STAT5 and Erk1/2 via its JM domain.NOK and EGFR synergistically promote proliferation and migration of breast cancer cells and induce tumorigenesis of normal cells.Co-expression of NOK and EGFR correlates with tumor malignant stages in breast cancer patients.
Synchronization of bowhead whales
Authors: Podolskiy Evgeny A. , Teilmann Jonas , Heide-Jørgensen Mads Peter 
Published: August 2024

Inferring animal behavior from irregular tracking data is a challenging area of research. It is particularly difficult to determine if whales, who intermittently explore different depths while staying in the same acoustic medium, synchronize their days with their prey and each other over kilometer-scale distances. Here, we aim to better understand the diving behavior of bowhead whales () in Disko Bay, West Greenland, using the largest high-frequency dive-depth dataset to date (144 days at 1 Hz from 12 different whales) and nonlinear dynamics, whereby we consider the whales to be chaotic (aperiodic) oscillators. We find that foraging whales dive deeper during the daytime in spring, with this diving behavior being in apparent synchrony with their vertically migrating prey. Furthermore, we demonstrate that bowhead whales can synchronize their behavior with each other for up to a week while staying within a range of up to ∼100km. This discovery agrees with the acoustic herd theory of long-range signaling in baleen whales. On the other hand, the synchrony might emerge when animals experience similar ecological conditions, which are, however, difficult to name because targeted depths and locations were separated for hundreds of meters and tens of kilometers, respectively. In this paper, we identify a framework for studying the sociality and behavior of such chaotically moving, unrestrained marine animals and call for more simultaneous tagging campaigns.

Published by the American Physical Society
2024