bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scar matrix drives Piezo1 mediated stromal inflammation leading to placenta accreta spectrum
Authors: Wenqiang Du , Novin Ashkan , Liu Yamin , Afzal Junaid , Suhail Yasir , Liu Shaofei , Gavin Nicole R. , Jorgensen Jennifer R. , Morosky Christopher M. , Figueroa Reinaldo , Schmidt Tannin A. , Sanders Melinda , Brewer Molly A. , Kshitiz  
Published: September 2024

AbstractScar tissue formation is a hallmark of wound repair in adults and can chronically affect tissue architecture and function. To understand the general phenomena, we sought to explore scar-driven imbalance in tissue homeostasis caused by a common, and standardized surgical procedure, the uterine scar due to cesarean surgery. Deep uterine scar is associated with a rapidly increasing condition in pregnant women, placenta accreta spectrum (PAS), characterized by aggressive trophoblast invasion into the uterus, frequently necessitating hysterectomy at parturition. We created a model of uterine scar, recapitulating PAS-like invasive phenotype, showing that scar matrix activates mechanosensitive ion channel, Piezo1, through glycolysis-fueled cellular contraction. Piezo1 activation increases intracellular calcium activity and Protein kinase C activation, leading to NF-κB nuclear translocation, and MafG stabilization. This inflammatory transformation of decidua leads to production of IL-8 and G-CSF, chemotactically recruiting invading trophoblasts towards scar, initiating PAS. Our study demonstrates aberrant mechanics of scar disturbs stroma-epithelia homeostasis in placentation, with implications in cancer dissemination.
Telomere-to-telomere assemblies of cattle and sheep Y-chromosomes uncover divergent structure and gene content
Authors: Olagunju Temitayo A. , Rosen Benjamin D. , Neibergs Holly L. , Becker Gabrielle M. , Davenport Kimberly M. , Elsik Christine G. , Hadfield Tracy S. , Koren Sergey , Kuhn Kristen L. , Rhie Arang , Shira Katie A. , Skibiel Amy L. , Stegemiller Morgan R. , Thorne Jacob W. , Villamediana Patricia , Cockett Noelle E. , Murdoch Brenda M. , Smith Timothy P. L. 
Published: September 2024

AbstractReference genomes of cattle and sheep have lacked contiguous assemblies of the sex-determining Y chromosome. Here, we assemble complete and gapless telomere to telomere (T2T) Y chromosomes for these species. We find that the pseudo-autosomal regions are similar in length, but the total chromosome size is substantially different, with the cattle Y more than twice the length of the sheep Y. The length disparity is accounted for by expanded ampliconic region in cattle. The genic amplification in cattle contrasts with pseudogenization in sheep suggesting opposite evolutionary mechanisms since their divergence 19MYA. The centromeres also differ dramatically despite the close relationship between these species at the overall genome sequence level. These Y chromosomes have been added to the current reference assemblies in GenBank opening new opportunities for the study of evolution and variation while supporting efforts to improve sustainability in these important livestock species that generally use sire-driven genetic improvement strategies.
Mechanical force regulates ligand binding and function of PD-1
Authors: Li Kaitao , Cardenas-Lizana Paul , Lyu Jintian , Kellner Anna V. , Li Menglan , Cong Peiwen , Watson Valencia E. , Yuan Zhou , Ahn Eunseon , Doudy Larissa , Li Zhenhai , Salaita Khalid , Ahmed Rafi , Zhu Cheng 
Published: September 2024

AbstractDespite the success of PD-1 blockade in cancer therapy, how PD-1 initiates signaling remains unclear. Soluble PD-L1 is found in patient sera and can bind PD-1 but fails to suppress T cell function. Here, we show that PD-1 function is reduced when mechanical support on ligand is removed. Mechanistically, cells exert forces to PD-1 and prolong bond lifetime at forces <7 pN (catch bond) while accelerate dissociation at forces >8pN (slip bond). Molecular dynamics of PD-1–PD-L2 complex suggests force may cause relative rotation and translation between the two molecules yielding distinct atomic contacts not observed in the crystal structure. Compared to wild-type, PD-1 mutants targeting the force-induced distinct interactions maintain the same binding affinity but suppressed/eliminated catch bond, lowered rupture force, and reduced inhibitory function. Our results uncover a mechanism for cells to probe the mechanical support of PD-1–PD-Ligand bonds using endogenous forces to regulate PD-1 signaling.
Spatial organization of adenylyl cyclase and its impact on dopamine signaling in neurons
Authors: Ripoll Léa , Li Yong , Dessauer Carmen W. , von Zastrow Mark 
Published: September 2024

AbstractThe cAMP cascade is increasingly recognized to transduce physiological effects locally through spatially limited cAMP gradients. However, little is known about how adenylyl cyclase enzymes that initiate cAMP gradients are localized. Here we address this question in physiologically relevant striatal neurons and investigate how AC localization impacts downstream signaling function. We show that the major striatal AC isoforms are differentially sorted between ciliary and extraciliary domains of the plasma membrane, and that one isoform, AC9, is uniquely concentrated in endosomes. We identify key sorting determinants in the N-terminal cytoplasmic domain responsible for isoform-specific localization. We further show that AC9-containing endosomes accumulate activated dopamine receptors and form an elaborately intertwined network with juxtanuclear PKA stores bound to Golgi membranes. Finally, we provide evidence that endosomal localization enables AC9 to selectively elevate PKA activity in the nucleus relative to the cytoplasm. Together, these results reveal a precise spatial landscape of the cAMP cascade in neurons and a key role of AC localization in directing downstream PKA signaling to the nucleus.
Cooperative chemoenzymatic and biocatalytic cascades to access chiral sulfur compounds bearing C(sp3)–S stereocentres
Authors: Zhao Fei , Mattana Ariane , Alam Ruqaiya , Montgomery Sarah L. , Pandya Akash , Manetti Fabrizio , Dominguez Beatriz , Castagnolo Daniele 
Published: September 2024

AbstractBiocatalysis has been widely employed for the generation of carbon-carbon/heteroatom stereocentres, yet its application in chiral C(sp3)–S bond construction is rare and limited to enzymatic kinetic resolutions. Herein, we describe the enantioselective construction of chiral C(sp3)–S bonds through ene-reductase biocatalyzed conjugate reduction of prochiral vinyl sulfides. A series of cooperative sequential/concurrent chemoenzymatic and biocatalytic cascades have been developed to access a broad range of chiral sulfides, including valuable β-hydroxysulfides bearing two adjacent C(sp3)–S and C(sp3)–O stereocentres, in a stereoconvergent manner with good to excellent yields (up to 96%) and enantioselectivities (up to >99% ee). Notably, this biocatalytic strategy allows to overcome the long-standing shortcomings of catalyst poisoning and C(sp2)/C(sp3)–S bond cleavage faced in transition-metal-catalyzed hydrogenation of vinyl sulfides. Finally, the potential of this methodology is also exemplified by its broader application in the stereoconvergent assembly of chiral C(sp3)–N/O/Se bonds with good to excellent enantioselctivities.
Impact of six-month COVID-19 travel moratorium on Plasmodium falciparum prevalence on Bioko Island, Equatorial Guinea
Authors: Hergott Dianna E. B. , Guerra Carlos A. , García Guillermo A. , Mba Eyono Jeremías Nzamío , Donfack Olivier T. , Iyanga Marcos Mbulito , Nguema Avue Restituto Mba , Abeso Nsegue Crisantos Nsue , Ondo Mifumu Teresa Ayingono , Rivas Matilde Riloha , Phiri Wonder P. , Murphy Sean C. , Guthrie Brandon L. , Smith David L. , Balkus Jennifer E. 
Published: September 2024

AbstractImportation of malaria infections is a suspected driver of sustained malaria prevalence on areas of Bioko Island, Equatorial Guinea. Quantifying the impact of imported infections is difficult because of the dynamic nature of the disease and complexity of designing a randomized trial. We leverage a six-month travel moratorium in and out of Bioko Island during the initial COVID-19 pandemic response to evaluate the contribution of imported infections to malaria prevalence on Bioko Island. Using a difference in differences design and data from island wide household surveys conducted before (2019) and after (2020) the travel moratorium, we compare the change in prevalence between areas of low historical travel to those with high historical travel. Here, we report that in the absence of a travel moratorium, the prevalence of infection in high travel areas was expected to be 9% higher than observed, highlighting the importance of control measures that target imported infections.
Doping strategy in metavalently bonded materials for advancing thermoelectric performance
Authors: Liu Ming , Guo Muchun , Lyu Haiyan , Lai Yingda , Zhu Yuke , Guo Fengkai , Yang Yueyang , Yu Kuai , Dong Xingyan , Liu Zihang , Cai Wei , Wuttig Matthias , Yu Yuan , Sui Jiehe 
Published: September 2024

AbstractMetavalent bonding is a unique bonding mechanism responsible for exceptional properties of materials used in thermoelectric, phase-change, and optoelectronic devices. For thermoelectrics, the desired performance of metavalently bonded materials can be tuned by doping foreign atoms. Incorporating dopants to form solid solutions or second phases is a crucial route to tailor the charge and phonon transport. Yet, it is difficult to predict if dopants will form a secondary phase or a solid solution, which hinders the tailoring of microstructures and material properties. Here, we propose that the solid solution is more easily formed between metavalently bonded solids, while precipitates prefer to exist in systems mixed by metavalently bonded and other bonding mechanisms. We demonstrate this in a metavalently bonded GeTe compound alloyed with different sulfides. We find that S can dissolve in the GeTe matrix when alloyed with metavalently bonded PbS. In contrast, S-rich second phases are omnipresent via alloying with covalently bonded GeS and SnS. Benefiting from the reduced phonon propagation and the optimized electrical transport properties upon doping PbS in GeTe, a high figure-of-merit ZT of 2.2 at 773 K in (Ge0.84Sb0.06Te0.9)(PbSe)0.05(PbS)0.05 is realized. This strategy can be applied to other metavalently bonded materials to design properties beyond thermoelectrics.
Strongly deleterious mutations influence reproductive output and longevity in an endangered population
Authors: Hasselgren Malin , Dussex Nicolas , von Seth Johanna , Angerbjörn Anders , Dalén Love , Norén Karin 
Published: September 2024

AbstractInbreeding depression has been documented in various fitness traits in a wide range of species and taxa, however, the mutational basis is not yet well understood. We investigate how putatively deleterious variation influences fitness and is shaped by individual ancestry by re-sequencing complete genomes of 37 individuals in a natural arctic fox (Vulpes lagopus) population subjected to both inbreeding depression and genetic rescue. We find that individuals with high proportion of homozygous loss of function genotypes (LoFs), which are predicted to exert a strong effect on fitness, generally have lower lifetime reproductive success and live shorter lives compared with individuals with lower proportion of LoFs. We also find that juvenile survival is negatively associated with the proportion of homozygous missense genotypes and positively associated with genome wide heterozygosity. Our results demonstrate that homozygosity of strongly and moderately deleterious mutations can be an important cause of trait specific inbreeding depression in wild populations, and mark an important step towards making more informed decisions using applied conservation genetics.
Taxometer: Improving taxonomic classification of metagenomics contigs
Authors: Kutuzova Svetlana , Nielsen Mads , Piera Pau , Nissen Jakob Nybo , Rasmussen Simon 
Published: September 2024

AbstractFor taxonomy based classification of metagenomics assembled contigs, current methods use sequence similarity to identify their most likely taxonomy. However, in the related field of metagenomic binning, contigs are routinely clustered using information from both the contig sequences and their abundance. We introduce Taxometer, a neural network based method that improves the annotations and estimates the quality of any taxonomic classifier using contig abundance profiles and tetra-nucleotide frequencies. We apply Taxometer to five short-read CAMI2 datasets and find that it increases the average share of correct species-level contig annotations of the MMSeqs2 tool from 66.6% to 86.2%. Additionally, it reduce the share of wrong species-level annotations in the CAMI2 Rhizosphere dataset by an average of two-fold for Metabuli, Centrifuge, and Kraken2. Futhermore, we use Taxometer for benchmarking taxonomic classifiers on two complex long-read metagenomics data sets where ground truth is not known. Taxometer is available as open-source software and can enhance any taxonomic annotation of metagenomic contigs.
Engineered allogeneic T cells decoupling T-cell-receptor and CD3 signalling enhance the antitumour activity of bispecific antibodies
Authors: Kapetanovic Edo , Weber Cédric R. , Bruand Marine , Pöschl Daniel , Kucharczyk Jakub , Hirth Elisabeth , Dietsche Claudius , Khan Riyaz , Wagner Bastian , Belli Olivier , Vazquez-Lombardi Rodrigo , Castellanos- Rueda Rocío , Di Roberto Raphael B. , Kalinka Kevin , Raess Luca , Ly Kevin , Rai Shivam , Dittrich Petra S. , Platt Randall J. , Oricchio Elisa , Reddy Sai T. 
Published: September 2024

AbstractBispecific antibodies (biAbs) used in cancer immunotherapies rely on functional autologous T cells, which are often damaged and depleted in patients with haematological malignancies and in other immunocompromised patients. The adoptive transfer of allogeneic T cells from healthy donors can enhance the efficacy of biAbs, but donor T cells binding to host-cell antigens cause an unwanted alloreactive response. Here we show that allogeneic T cells engineered with a T-cell receptor that does not convert antigen binding into cluster of differentiation 3 (CD3) signalling decouples antigen-mediated T-cell activation from T-cell cytotoxicity while preserving the surface expression of the T-cell-receptor–CD3 signalling complex as well as biAb-mediated CD3 signalling and T-cell activation. In mice with CD19+ tumour xenografts, treatment with the engineered human cells in combination with blinatumomab (a clinically approved biAb) led to the recognition and clearance of tumour cells in the absence of detectable alloreactivity. Our findings support the development of immunotherapies combining biAbs and ‘off-the-shelf’ allogeneic T cells.
Feasible deployment of carbon capture and storage and the requirements of climate targets
Authors: Kazlou Tsimafei , Cherp Aleh , Jewell Jessica 
Published: September 2024

AbstractClimate change mitigation requires the large-scale deployment of carbon capture and storage (CCS). Recent plans indicate an eight-fold increase in CCS capacity by 2030, yet the feasibility of CCS expansion is debated. Using historical growth of CCS and other policy-driven technologies, we show that if plans double between 2023 and 2025 and their failure rates decrease by half, CCS could reach 0.37 GtCO2 yr−1 by 2030—lower than most 1.5 °C pathways but higher than most 2 °C pathways. Staying on-track to 2 °C would require that in 2030–2040 CCS accelerates at least as fast as wind power did in the 2000s, and that after 2040, it grows faster than nuclear power did in the 1970s to 1980s. Only 10% of mitigation pathways meet these feasibility constraints, and virtually all of them depict <600 GtCO2 captured and stored by 2100. Relaxing the constraints by assuming no failures of CCS plans and growth as fast as flue-gas desulfurization would approximately double this amount.
Climate variability shifts the vertical structure of phytoplankton in the Sargasso Sea
Authors: Viljoen Johannes J. , Sun Xuerong , Brewin Robert J. W. 
Published: September 2024

AbstractMarine phytoplankton are essential to ocean biogeochemical cycles. However, our understanding of changes in phytoplankton rely largely on satellite data, which can only assess changes in surface phytoplankton. How climate variability is impacting their vertical structure remains unclear. Here we use 33 years’ worth of data from the Sargasso Sea to show distinct seasonal and long-term phytoplankton climate responses in the surface mixed layer compared with the subsurface. Seasonally, the surface community alters their carbon-to-chlorophyll ratio without changing their carbon biomass, whereas the chlorophyll a and carbon of the subsurface community covaries with no change in their carbon-to-chlorophyll ratio. Over the last decade, the subsurface phytoplankton biomass has increased in response to warming, whereas the surface phytoplankton have altered their carbon-to-chlorophyll ratio with minimal change in their carbon biomass. Given that satellites can only view the surface ocean, sustained subsurface monitoring is required to provide a full understanding of how phytoplankton are responding to climate change.
Genomic and fitness consequences of a near-extinction event in the northern elephant seal
Authors: Hoffman Joseph I. , Vendrami David L. J. , Hench Kosmas , Chen Rebecca S. , Stoffel Martin A. , Kardos Marty , Amos William , Kalinowski Jörn , Rickert Daniel , Köhrer Karl , Wachtmeister Thorsten , Goebel Mike E. , Bonin Carolina A. , Gulland Frances M. D. , Dasmahapatra Kanchon K. 
Published: September 2024

AbstractUnderstanding the genetic and fitness consequences of anthropogenic bottlenecks is crucial for biodiversity conservation. However, studies of bottlenecked populations combining genomic approaches with fitness data are rare. Theory predicts that severe bottlenecks deplete genetic diversity, exacerbate inbreeding depression and decrease population viability. However, actual outcomes are complex and depend on how a species’ unique demography affects its genetic load. We used population genetic and veterinary pathology data, demographic modelling, whole-genome resequencing and forward genetic simulations to investigate the genomic and fitness consequences of a near-extinction event in the northern elephant seal. We found no evidence of inbreeding depression within the contemporary population for key fitness components, including body mass, blubber thickness and susceptibility to parasites and disease. However, we detected a genomic signature of a recent extreme bottleneck (effective population size = 6; 95% confidence interval = 5.0–7.5) that will have purged much of the genetic load, potentially leading to the lack of observed inbreeding depression in our study. Our results further suggest that deleterious genetic variation strongly impacted the post-bottleneck population dynamics of the northern elephant seal. Our study provides comprehensive empirical insights into the intricate dynamics underlying species-specific responses to anthropogenic bottlenecks.
Dataset from a human-in-the-loop approach to identify functionally important protein residues from literature
Authors: Vollmar Melanie , Tirunagari Santosh , Harrus Deborah , Armstrong David , Gáborová Romana , Gupta Deepti , Afonso Marcelo Querino Lima , Evans Genevieve , Velankar Sameer 
Published: September 2024

AbstractWe present a novel system that leverages curators in the loop to develop a dataset and model for detecting structure features and functional annotations at residue-level from standard publication text. Our approach involves the integration of data from multiple resources, including PDBe, EuropePMC, PubMedCentral, and PubMed, combined with annotation guidelines from UniProt, and LitSuggest and HuggingFace models as tools in the annotation process. A team of seven annotators manually curated ten articles for named entities, which we utilized to train a starting PubmedBert model from HuggingFace. Using a human-in-the-loop annotation system, we iteratively developed the best model with commendable performance metrics of 0.90 for precision, 0.92 for recall, and 0.91 for F1-measure. Our proposed system showcases a successful synergy of machine learning techniques and human expertise in curating a dataset for residue-level functional annotations and protein structure features. The results demonstrate the potential for broader applications in protein research, bridging the gap between advanced machine learning models and the indispensable insights of domain experts.
A starfish-inspired 4D self-healing morphing structure
Authors: Raman  , Labisch Susanna , Dirks Jan-Henning 
Published: September 2024

AbstractInspired by the starfish's unique ability to achieve flexibility and posture-holding with minimal energy expenditure, we present a novel bioinspired morphing structure. Our two-component design, consisting of a thermoplastic mesh and elastomeric jacket, effectively mimics the functions of the starfish's ossicles, mutable collagenous tissues, and derma. This structure exhibits a remarkable combination of self-healing, time-dependent shape memory, and self-posture-holding properties. Systematic variations in mesh geometry demonstrate precise control over structural stiffness and thermal response, enabling customization for specific applications. The structure's scalability and ease of fabrication further enhance its adaptability. We experimentally demonstrate the potential of our biomimetic morphing structure using several prototypes. This work lays the foundation for developing a new type of versatile morphing structures with applications in diverse fields, including robotics, biomedical devices, and adaptive structures.
The use of accelerometers to assess upper limb function in patients with obstetric brachial plexus palsy
Authors: Leypold Tim , Bahm Jörg , Schäfer Benedikt , Beier Justus P. , Disselhorst-Klug Catherine , Fonseca-Höflinger Ligia C. 
Published: September 2024

AbstractFor half a century, the Mallet Scale (MS) has been utilized to assess upper limb function in patients with obstetric brachial plexus palsy (OBPP). However, the correct use of the MS requires trained personnel and the MS does not measure compensatory movements. For this reason, new methods are needed to compensate for these weaknesses. This study introduces an innovative method for objective functional motion analysis using accelerometers to measure upper limb movements in thirty patients with obstetric brachial plexus lesions. Five triaxial accelerometers were positioned on the chest and each upper limb. They recorded acceleration signals during repetitive everyday tasks: hand-to-mouth (HM), hand-to-neck (HN), and hand-to-spine (HS). From these signals, 54 features were extracted and subjected to linear correlation tests to identify 5 suitable features. An algorithm was then developed to categorize patients into five groups and compute an individual movement performance score (iMPScore) assessing the patient’s upper extremity function. By using the iMPScore more than 75% of all participants have been classified correctly with respect to their MS category. Identification of MS I category patients in general and assessing upper extremity function of MS I to III in HS tasks were most challenging. We conclude that the introduced approach is a valuable tool for gauging movement limitation of upper limbs in patients with obstetric brachial plexus palsy. Compared to other clinically established methods, it becomes possible to record and even quantify the extent of compensatory movements. In this way, an objective, user- and patient-friendly method is offered, which supports significantly physicians and therapists in their evaluation of OBPP.