bluuebunny/crossref_metadata_2025_split huggingface dataset:
Explaining tip-of-the-tongue experiences in older adults – contributions of brain function, structure, and perfusion in relation to older adults’ cardiorespiratory fitness
Authors: Rahman Foyzul , Tsvetanov Kamen A. , Feron Jack , Mullinger Karen , Joyce Kelsey , Gilani Ahmed , Fernandes Eunice G. , Wetterlin Allison , Wheeldon Linda , Lucas Samuel J.E. , Segaert Katrien 
Published: December 2023

AbstractCognitive decline associated with healthy ageing is complex and multifactorial: brain-based and lifestyle factors uniquely and jointly contribute to distinct neurocognitive trajectories of ageing. To evaluate existing models of neurocognitive ageing such as compensation, maintenance, or reserve, we explore how various known brain-based and cardiorespiratory fitness factors intersect to better understand cognitive decline. We tested 73 (Mage= 65.51) neurologically healthy older adults and collected neuroimaging (functional, structural, and perfusion MRI), cardiorespiratory fitness, and behavioural performance data to investigate a well-documented, prominent cognitive challenge for older adults: word-finding failures. We aimed to uncover associations between predictors, which have previously been theoretically-implicated, in explaining age-related tip-of-the-tongue rates. Commonality analyses revealed that functional activation of language networks associated with tip-of-the-tongue states is in part linked with age and, interestingly, cardiorespiratory fitness levels. Age-associated atrophy and perfusion in regions other than those showing functional differences accounted for variance in tip-of-the-tongue states. Our findings can be interpreted in the context of the classic models of neurocognitive ageing suggesting compensation. Our findings moreover suggest that brain health indices in concordance with cardiorespiratory fitness measures have the potential to provide a more holistic explanation of individual differences in age-related cognitive decline.HighlightsThe incidence of word-finding failures is associated with brain health and cardiorespiratory fitness factorsLanguage network activation associated with word-finding failures is linked to age and cardiorespiratory fitness levelsDistinct contribution of brain structure and perfusion are also associated with word-findingBrain health indices in concordance with cardiorespiratory fitness measures have the potential to provide a more holistic explanation of individual differences in age-related cognitive decline
Microbial metabolic specificity controls pelagic lipid export efficiency
Authors: Behrendt Lars , Alcolombri Uria , Hunter Jonathan E. , Smriga Steven , Mincer Tracy , Lowenstein Daniel P. , Yawata Yutaka , Peaudecerf François J. , Fernandez Vicente I. , Fredricks Helen F. , Almblad Henrik , Harrison Joe J. , Stocker Roman , Van Mooy Benjamin A. S. 
Published: December 2023

AbstractLipids comprise more than 20% of sinking organic matter in the ocean and play a crucial role in the carbon cycle. Despite this, our understanding of the processes that control lipid degradation is limited. Here we combined nano-lipidomics and imaging to study the bacterial degradation of diverse algal lipid droplets. Bacteria isolated from natural marine particles exhibited distinct dietary preferences, ranging from selective to promiscuous degraders. Dietary preference was associated with a distinct set of lipid degradation genes rather than with taxonomic origin. The top degrader,Pseudomonas zhaodongensis,rapidly consumed triacylglycerols (TAGs) from lipid extracts while promoting colonization of kin by chemotaxis toward glycerol, the TAG degradation product. Using synthetic communities composed of isolates with distinct dietary preferences, we demonstrated that lipid degradation is modulated by microbial interactions. A particle export model incorporating these dynamics suggests that metabolic specialization and community dynamics influences lipid transport efficiency in the ocean’s mesopelagic zone.
Spatial Patterning Analysis of Cellular Ensembles (SPACE) discovers complex spatial organization at the cell and tissue levels
Authors: Schrom Edward C. , McCaffrey Erin F. , Sreejithkumar Vivek , Radtke Andrea J. , Ichise Hiroshi , Arroyo-Mejias Armando , Speranza Emily , Arakkal Leanne , Thakur Nishant , Grant Spencer , Germain Ronald N. 
Published: December 2023

AbstractSpatial patterns of cells and other biological elements drive both physiologic and pathologic processes within tissues. While many imaging and transcriptomic methods document tissue organization, discerning these patterns is challenging, especially when they involve multiple elements in complex arrangements. To address this challenge, we present Spatial Patterning Analysis of Cellular Ensembles (SPACE), an R package for analysis of high-plex spatial data. SPACE is compatible with any data collection modality that records values (i.e., categorical cell/structure types or quantitative expression levels) at fixed spatial coordinates (i.e., 2d pixels or 3d voxels). SPACE detects not only broad patterns of co-occurrence but also context-dependent associations, quantitative gradients and orientations, and other organizational complexities. Via a robust information theoretic framework, SPACE explores all possible ensembles of tissue elements – single elements, pairs, triplets, and so on – and ranks the most strongly patterned ensembles. For single images, rankings reflect patterns that differ from random assortment. For sets of images, rankings reflect patterns that differ across sample groups (e.g., genotypes, treatments, timepoints, etc.). Further tools then thoroughly characterize the nature of each pattern for intuitive interpretation. We validate SPACE and demonstrate its advantages using murine lymph node images for which ground truth has been defined. We then use SPACE to detect new patterns across varied datasets, including tumors and tuberculosis granulomas.
ATAT: Automated Tissue Alignment and Traversal in Spatial Transcriptomics with Self-Supervised Learning
Authors: Song Steven , Mohsin Emaan , Zhang Renyu , Kuznetsov Andrey , Shen Le , Grossman Robert L. , Weber Christopher R. , Khan Aly A. 
Published: December 2023

AbstractSpatial transcriptomics (ST) has enhanced RNA analysis in tissue biopsies, but interpreting these data is challenging without expert input. We present Automated Tissue Alignment and Traversal (ATAT), a novel computational framework designed to enhance ST analysis in the context of multiple and complex tissue architectures and morphologies, such as those found in biopsies of the gastrointestinal tract. ATAT utilizes self-supervised contrastive learning on hematoxylin and eosin (H&E) stained images to automate the alignment and traversal of ST data. This approach addresses a critical gap in current ST analysis methodologies, which rely heavily on manual annotation and pathologist expertise to delineate regions of interest for accurate gene expression modeling. Our framework not only streamlines the alignment of multiple ST samples, but also demonstrates robustness in modeling gene expression transitions across specific regions. Additionally, we highlight the ability of ATAT to traverse complex tissue topologies in real-world cases from various individuals and conditions. Our method successfully elucidates differences in immune infiltration patterns across the intestinal wall, enabling the modeling of transcriptional changes across histological layers. We show that ATAT achieves comparable performance to the state-of-the-art method, while alleviating the burden of manual annotation and enabling alignment of tissue samples with complex morphologies.AvailabilityATAT is available at:https://github.com/StevenSong/tissue-alignment
Bone quality following peripubertal growth in a mouse model of transmasculine gender-affirming hormone therapy
Authors: Henry Brandon W. , Cruz Cynthia Dela , Goulet Robert W. , Nolan Bonnie T. , Locke Conor , Padmanabhan Vasantha , Moravek Molly B. , Shikanov Ariella , Killian Megan L. 
Published: December 2023

AbstractDuring peri-puberty, bone growth and the attainment peak bone mass is driven predominantly by sex steroids. This is important when treating transgender and gender diverse youth, who have become increasingly present at pediatric clinics. Analogues of gonadotropin-releasing hormone (GnRH) are commonly prescribed to transgender and gender diverse youth prior to starting gender-affirming hormone therapy (GAHT). However, the impact of GnRH agonists on long bones with the addition of GAHT is relatively unknown. To explore this, we developed a trans-masculine model by introducing either GnRHa or vehicle treatment to female-born mice at a pre-pubertal age. This treatment was followed by male GAHT (testosterone, T) or control treatment three weeks later. Six weeks after T therapy, bone quality was compared between four treatment groups: Control (vehicle only), GnRHa-only, GnRHa + T, and T-only. Bone length/size, bone shape, mechanical properties, and trabecular morphology were modulated by GAHT. Independent of GnRHa administration, mice treated with T had shorter femurs, larger trabecular volume and increased trabecular number, higher trabecular bone mineral density, and wider superstructures on the surface of bone (e.g., third trochanters) when compared to control or GnRHa-only mice. In conclusion, prolonged treatment of GnRHa with subsequent GAHT treatment directly affect the composition, parameters, and morphology of the developing long bone. These findings provide insight to help guide clinical approaches to care for transgender and gender diverse youth.
All-cause, circulatory disease and cancer mortality in the population of a large Italian area contaminated by perfluoroalkyl and polyfluoroalkyl substances (1980-2018)
Authors: Biggeri Annibale , Stoppa Giorgia , Facciolo Laura , Fin Giuliano , Mancini Silvia , Manno Valerio , Minelli Giada , Zamagni Federica , Zamboni Michela , Catelan Dolores , Bucchi Lauro 
Published: December 2023

AbstractBackgroundPerfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. A clear association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (north-eastern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018.MethodsThe Italian National Institute of Health and the Italian National Institute of Statistics made available the anonymous records of death certificates of residents of the provinces of Vicenza, Verona and Padova (males, n=29,629; females, n=29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardized (European standard population 2013) mortality ratios using the total population of the three provinces in the same calendar period as a reference. The birth cohort analysis was performed using cumulative risks for ages 20-84 years.ResultsDuring the 33 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of available cause-specific mortality), in the resident population of theRed area(the municipalities being connect to the contaminated water plant) we observed 51,621 deaths as compared to 47,731 expected (age-sex SMR: 108; 90% CI: 107-109). We found evidence of raised mortality for diseases of the circulatory system (in particular, heart disease and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer.ConclusionsFor the first time, an association of PFAS exposure with mortality from circulatory disease mortality was formally demonstrated. Circumstantial evidence regarding kidney cancer and testicular cancer is consistent with previously reported data.
A Fast Interferometric Beam Shaper for Multi-Emitter 3D MINFLUX
Authors: Geismann Maximilian K. , Gomez-Segalas Alba , Passera Alessandro , Shirzadian Mehrta , Balzarotti Francisco 
Published: December 2023

AbstractBeams of light that feature an intensity zero are essential to a variety of optical microscopy methods. Super-resolution techniques like STED and RESOLFT, together with localization strategies like MINFLUX and MINSTED, rely on accurate and fast displacements of such beams and their zeros. Extending these methods to the third dimension requires axial deflection, which, in contrast to lateral deflection, remains technologically challenging on the microsecond scale. Here, we present a fast general-purpose beam-shaping polarization interferometer that, instead of displacing the entire beam, enables such axial deflections by deforming the beam shape to deflect its zero. Based on this approach, we showcase a four-channel dual-color excitation system for three-dimensional MINFLUX imaging and tracking. We include first demonstrations of improved MINFLUX localization schemes that utilize the combination of distinct beam shapes and three-dimensional multi-emitter tracking. We believe that the presented approach will facilitate the broader adoption of three dimensional MINFLUX and provides a versatile basis for future implementations of advanced single-molecule localization methods.
Tissue stiffness mapping by light sheet elastography
Authors: Zhu Min , Zhang Kaiwen , Thomas Evan C. , Xu Ran , Ciruna Brian , Hopyan Sevan , Sun Yu 
Published: December 2023

ABSTRACTTissue stiffness plays a crucial role in regulating morphogenesis. The ability to measure and monitor the dynamic progression of tissue stiffness is important for generating and testing mechanistic hypotheses. Methods to measure tissue propertiesin vivohave been emerging but present challenges with spatial and temporal resolution especially in 3D, by their reliance on highly specialised equipment, and/or due to their invasive nature. Here, introduce light sheet elastography, a noninvasive method that couples low frequency shear waves with light sheet fluorescence microscopy by adapting commercially available instruments. With this method, we achievedin totostiffness mapping of organ-stage mouse and zebrafish embryos at cellular resolution. Versatility of the method enabled time-lapse stiffness mapping during tissue remodelling and of the beating embryonic heart. This method expands the spectrum of tools available to biologists and presents new opportunities for uncovering the mechanical basis of morphogenesis.
A novel nested geneAff3irparticipates in vascular remodelling by enhancing endothelial cell differentiation in mice
Authors: Zhao Yue , Ehteramyan Mazdak , Li Yi , Bai Xuefeng , Huang Lei , Gao Yingtang , Angbohang Angshumonik , Yang Xiaoping , Lynham Steven , Margariti Andriana , Shah Ajay M , Tao Yaling , Cai Ting , Li Tong , Zhang Min , Zeng Lingfang 
Published: December 2023

AbstractEndothelial integrity in the vasculature is critically maintained by vascular stem/progenitor cells (SPCs) giving rise to endothelial cells (ECs). However, the genes significantly activated during differentiation remain incompletely understood. Based on mouse aorta and vein cDNA library, we unearthed a hitherto unidentified gene nested residing within intron 6 ofAff3, christened asAff3intron resident (Aff3ir), upregulated during laminar shear stress-induced ECs differentiation in mouse. Proteomic analysis substantiated the presence of a 45-amino acid(aa) peptide (AFF3IR-ORF1) and 109-aa or 151-aa protein (AFF3IR-ORF2) encoded from two transcript variants. During embryonic development, AFF3IR-ORF1 peaked at E14.5, while AFF3IR-ORF2 displayed a continuous increase until E19.5. In adult mice, AFF3IR-ORF1 was detected in the lung, liver, spleen, and kidney, while AFF3IR-ORF2 was most abundant in the aorta. Furthermore, Western blot and immunofluorescence analyses revealed a specific upregulation of AFF3IR-ORF2, but not AFF3IR-ORF1, three days after femoral artery injury or hindlimb ischemiain vivo. Overexpression of AFF3IR-ORF2 enhanced, while its knockdown attenuated, SPCs differentiation into ECs induced by shear stress or vascular endothelial growth factorin vitro. Notably, the upregulated AFF3IR-ORF2 hindered SPCs proliferation by sequestering minichromosome maintenance complex component 3 in the cytoplasm, thereby shifting the status of SPCs from a pro-proliferation to a pro-differentiation state. In conclusion, our discoveries unveil the novel protein-coding geneAff3iras a participant in ECs differentiation, providing fresh insights into the regulation of vascular endothelial integrity.
Evolution of threat response-related polymorphisms at theSLC6A4locus in callitrichid primates
Authors: Twyman Hanlu , Heywood India , Barros Marília , Zeredo Jorge , Mundy Nicholas I. , Santangelo Andrea 
Published: December 2023

AbstractVariation in an upstream repetitive region at theSLC6A4locus, which encodes a serotonin transporter, is associated with anxiety-related behaviour in a few primate species, including humans and rhesus macaques. In this study we investigate evolution ofSLC6A4polymorphisms associated with anxiety-related behaviour in common marmosets (Callithrix jacchus). Assaying variation in theSLC6A4repeat region across 14 species in 8 genera of callitrichid primates (marmosets and tamarins) we find large interspecific variation in the number of repeats present (24-43). The black tufted-ear marmoset (C. penicillata) has sequence polymorphisms similar to those found in the common marmoset, which is its sister species, and no other species has intraspecific variation at these sites. We conclude that, similar to humans and rhesus macaques, the functional polymorphism atSLC6A4in common marmosets has a recent evolutionary origin, and that the anxiety-related allele is evolutionarily derived. Common/black tufted-ear marmosets and rhesus macaques share high ecological adaptability and behavioural flexibility that we propose may be related to the maintenance of the polymorphism.
Intestinal epithelialAtg16l1influences pregnancy-induced fecal microbiota shifts in mice
Authors: López-Agudelo Víctor A. , Falk-Paulsen Maren , Rehman Ateequr , Bharti Richa , Sommer Felix , Wacker Eike Matthias , Ellinghaus David , Luzius Anne , Sievers Laura , Kaser Arthur , Rosenstiel Philip 
Published: December 2023

SummaryThroughout gestation, the female body undergoes a series of transformations, including profound alterations in intestinal microbial communities. Changes gradually increase towards the end of pregnancy and comprise reduced α-diversity of microbial communities and an increased propensity for energy harvest. Despite the importance of the intestinal microbiota for the pathophysiology of inflammatory bowel diseases, very little is known about the relationship between these microbiota shifts and pregnancy-associated complications of the disease. Here, we explored the longitudinal dynamics of gut microbiota composition and functional potential during pregnancy and after lactation inAtg16l1ΔIECmice carrying an intestinal epithelial deletion of the Crohńs disease risk geneAtg16l1.Using 16S rRNA amplicon and shotgun metagenomic sequencing, we demonstrated divergent temporal shifts in microbial composition betweenAtg16l1wildtype andAtg16l1ΔIECpregnant mice in trimester 3, which was validated in an independent experiment. Observed differences included microbial genera implicated in IBD such asLachnospiraceae,Roseburia,Ruminococcus, andTuricibacter. Changes partially recovered after lactation. In addition, functional inference of metagenomic data suggest a reduced potential to biosynthesize mucosal protective polyamines and reduced capacity to metabolize acidic polysaccharides (ketogluconate metabolism).On the host side, we found that the immunological response ofAtg16l1ΔIECmice is characterized by higher colonic mRNA levels of TNFA, and CXCL1 in trimester 3 and a lower weight of offspring at birth. Understanding pregnancy-dependent microbiome changes in the context of IBD may constitute the first step in the identification of fecal microbial biomarkers and microbiota-directed therapies that could help improving precision care for managing pregnancies in IBD patients.
DSMBind: SE(3) denoising score matching for unsupervised binding energy prediction and nanobody design
Authors: Jin Wengong , Chen Xun , Vetticaden Amrita , Sarzikova Siranush , Raychowdhury Raktima , Uhler Caroline , Hacohen Nir 
Published: December 2023

AbstractModeling the binding between proteins and other molecules is pivotal to drug discovery. Geometric deep learning is a promising paradigm for protein-ligand/protein-protein binding energy prediction, but its accuracy is limited by the size of training data as high-throughput binding assays are expensive. Herein, we propose an unsupervised binding energy prediction framework, named DSMBind, which does not need experimental binding data for training. DSMBind is an energy-based model that estimates the likelihood of a protein complex via SE(3) denoising score matching (DSM). This objective, applied at both backbone and side-chain levels, builds on a novel equivariant rotation prediction network derived from Euler’s Rotation Equations. We find that the learned log-likelihood of protein complexes is highly correlated with experimental binding energy across multiple benchmarks, even matching the performance of supervised models trained on experimental data. We further demonstrate DSMBind’s zero-shot binder design capability through a PD-L1 nanobody design task, where we randomize all three complementarity-determining regions (CDRs) and select the best CDR sequences based on DSMBind score. We experimentally tested the designed nanobodies with ELISA binding assay and successfully discovered a novel PD-L1 binder. In summary, DSMBind offers a versatile framework for binding energy prediction and binder design. Our code is publicly available atgithub.com/wengong-jin/DSMBind.
Restriction of intercellular communication is required for organ regeneration
Authors: Cohen Itay , Hak Hagit , Perez-Sancho Jessica , Spiegelman Ziv , Efroni Idan 
Published: December 2023

AbstractThe excision of the root tip, including the stem cell niche, triggers rapid regeneration from remnant cells in the stump. In plants, cell identity relies on positional information transported through cytoplasmatic bridges known as plasmodesmata. However, how such information is reset to allow the regeneration of lost identities is unknown. Here, we show that the movement of mobile signals is temporarily restricted near the incision site and that regeneration-induced members of the LATERAL ORGAN DOMAIN (LBD) plant-specific developmental regulators are necessary and sufficient for this restriction. Regeneration was disrupted in high-orderlbdmutants but was restored by transient localized plasmodesmata closure. We propose that LBD-mediated modulation of intercellular connectivity is crucial for plant regeneration and may have widespread roles inde novopattern formation.One Sentence SummaryPlant-specific DNA binding genes mediate a transient restriction of intercellular communication to allow root regeneration