bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early founder effects have determined paternal population structure in the Faroe Islands
Authors: Mann Allison E. , Magnussen Eyðfinn , Tillquist Christopher R. 
Published: August 2024

AbstractThe Faroe Islands are a small archipelago located in the North Atlantic likely colonized by a small group of founders sometime between 50 and 300 CE. Post colonization, the Faroese people have been largely isolated from admixture with mainland and other island populations in the region. As such, the initial founder effect and subsequent genetic drift are likely major contributors to the modern genetic diversity found among the Faroese. In this study, we assess the utility of Y-chromosomal microsatellites to detect founder effect in the Faroe Islands through the construction of haplotype networks and a novel empirical method, mutational distance from modal haplotype histograms (MDM), for the visualization and evaluation of population bottlenecks. We compared samples from the Faroe Islands and Iceland to possible regional source populations and documented a loss of diversity associated with founder events. Additionally, within-haplogroup diversity statistics reveals lower haplotype diversity and richness within both the Faroe Islands and Iceland, consistent with a small founder population colonizing both regions. However, in the within-haplogroup networks, the Faroe Islands are found within the larger set of potential source populations while Iceland is consistently found on isolated branches. Moreover, comparisons of within-haplogroup MDM histograms document a clear founder signal in the Faroes and Iceland, but the strength of this signal is haplogroup-dependent which may be indicative of more recent admixture or other demographic processes. The results of the current study and lack of conformity between Icelandic and Faroese haplotypes implies that the two populations were founded by different paternal gene pools and there is no detectable post-founder admixture between the two groups.
Characterisation of coastal reef fish assemblages across an estuarine-urbanisation gradient using underwater visual survey and environmental DNA metabarcoding
Authors: Pei Yu-De , Heard Joseph , Xu Wenqian , Leung Shara K. K. , Yung Charmaine C. M. , Wyatt Alex S. J. 
Published: August 2024

AbstractThe ongoing urbanisation of coastlines around the globe jeopardises biodiversity, including coastal marine fishes. In many places, baseline data on fish communities are inadequate for understanding the ecological and conservation impacts of this urbanisation. Here, we document spatiotemporal patterns in fish diversity (at genus level) across an estuarine gradient around Hong Kong, a highly urbanised coastal megacity bordering the estuary of the Pearl River, the second largest river in the People’s Republic of China. We combined underwater visual census (UVC) with eDNA metabarcoding (eDNA) to overcome challenges associated with the high turbidity of Hong Kong’s aquatic environment that limits the capacity for visual observations. Similar to previous studies, UVC and eDNA captured different components of the fish community, sharing only 36.5 % fish genera in common. Nevertheless, we recorded 17 % of the known fish diversity and provided a comprehensive picture of patterns in fish diversity across the gradient, despite limited sampling effort. Fish richness was reduced by 1.6-to 3-fold under the highly turbid estuarine conditions found around Lantau compared to other regions. However, overall, there were only moderate changes in the fish community regionally. Seasonal variations in fish richness and assemblage structure were observed using both approaches, taken to reflect changes in fish behaviour, physiology, and naturally occurring events (i.e., spawning and recruitment) between seasons. A notable, consistent reduction in eDNA richness in the semi-enclosed Port Shelter might reflect limited exchange of water and genetic materials. A total of eleven species that had not been previously reported from Hong Kong were detected. These potentially novel species, as well as other ecologically and economically important species in Hong Kong, might be insufficiently protected from unregulated fishing activities due to the limited spatial coverage of marine protected areas.
Focused Ultrasound Augments the Delivery and Penetration of Model Therapeutics into Cerebral Cavernous Malformations
Authors: Fisher Delaney G. , Hoch Matthew R. , Gorick Catherine M. , Huchthausen Claire , Breza Victoria R. , Sharifi Khadijeh A. , Tvrdik Petr , Miller G. Wilson , Price Richard J. 
Published: August 2024

AbstractBACKGROUNDCerebral cavernous malformations (CCMs) are vascular neoplasms in the brain that can cause debilitating symptoms. Current treatments pose significant risks to some patients, motivating the development of new nonsurgical options. We recently discovered that focused ultrasound-microbubble treatment (FUS) arrests CCM formation and growth. Here, we build on this discovery and assess the ability of FUS to deliver model therapeutics into CCMs.METHODSQuantitative T1 mapping MRI sequences were used with 1 kDa (MultiHance; MH) and 17 kDa (GadoSpin D; GDS) contrast agents to assess the FUS-mediated delivery and penetration of model small molecule drugs and biologics, respectively, into CCMs of Krit1 mutant mice.RESULTSFUS elevated the rate of MH delivery to both the lesion core (4.6-fold) and perilesional space (6.7-fold). Total MH delivery more than doubled in the lesion core and tripled in the perilesional space when FUS was applied immediately prior to MH injection. For the model biologic drug (i.e. GDS), FUS was of greater relative benefit, resulting in 21.7-fold and 3.8-fold delivery increases to the intralesional and perilesional spaces, respectivelyCONCLUSIONSFUS augments the delivery and penetration of therapeutics into the complex and disorganized CCM microenvironment. Benefits to small molecule drug delivery are more evident in the perilesional space, while benefits to biologic delivery are more evident in CCM cores. These findings, when combined with ability of FUS alone to control CCMs, highlight the potential of FUS to serve as a powerful non-invasive therapeutic platform for CCM.
Neuronal heterogeneity in the medial septum and diagonal band of Broca: classes and continua
Authors: Kuhn Felix , Mocellin Petra , Pupe Stefano , Wang Lihua , Lemire Andrew L. , Sosulina Liudmila , Barnstedt Oliver , Spruston Nelson , Cembrowski Mark S. , Remy Stefan 
Published: August 2024

SUMMARYThe medial septum and diagonal band of Broca (MSDB) is known for its diverse populations of cholinergic, GABAergic, and glutamatergic neurons, each contributing to various cognitive processes. However, cell-specific manipulations within this region often result in incongruous behavioral outcomes and reach conflicting conclusions, likely because of a hitherto unknown molecular complexity in its cellular landscape. In this study, we employed single-cell RNA sequencing to thoroughly describe the heterogeneity of MSDB neurons. We confirmed previously established neuronal classes, found gene expression gradients within them and revealed genetically defined subclusters. Moreover, we characterized the genetic profiles of these neuronal subclusters and mapped their spatial distribution. Our analysis presents a comprehensive description of the heterogeneity of MSDB neurons, provides marker genes to target them, explains previous paradoxical results, and opens unexplored avenues to study the impact of neuromodulators in the basal forebrain.
Birth order specified recruitment of motor circuits during spontaneous neural activity in zebrafish embryo
Authors: Abi Younes Maroun , Rima Mohamad , Coutanceau Jean-Pierre , Peysson Ninon , Hoseinkhani Fatemeh , Rodrigues Edson , Bullier Erika , Legendre Pascal , Mangin Jean-Marie , Hong Elim 
Published: August 2024

SummaryModular organization of spinal neural circuits control dynamic regulation of locomotion. However, it is unknown when or how the distinct microcircuits emerge during development. We carried out high-resolution calcium imaging of neural activity driving the first motor behavior in one day old zebrafish embryo. During this period, at least two waves of neurogenesis occur to generate primary and secondary motoneurons. We found that embryos first display a single highly synchronized rhythmic neuronal circuit containing interneurons and motoneurons. Later, two distinct interneuron-motoneuron circuits emerge with one containing early-born motoneurons displaying low-frequency activity and the other containing later-born motoneurons with high-frequency activity. The results indicate a mode of birth order determined microcircuits where neurons that are born together are recruited together. Nicotine affected neuronal activity frequency, revealing a functional role for cholinergic signaling in the emergence of patterned spinal circuits. Indeed, we found aberrant arrhythmic synchronized activity in mutants forcholineacetyltransferase-awhere acetylcholine is no longer synthesized. Overall, we reveal the sequential recruitment of birth order specified microcircuits during the emergence of the earliest motor behavior and highlight a conserved role for cholinergic signaling in regulating rhythmic neural activity in the embryonic spinal cord.
Phylogenetic diversity of light dependent phosphorylation of Thr78 in Rca
Authors: Bhatnagar Nikita , Chung Sarah S. , Hodge John , Boyd Ryan A , Kim Sang Yeol , Sands Mia , Leakey Andrew D. B. , Ort Donald R. , Burgess Steven 
Published: August 2024

SUMMARYRubisco activase is an ATP-dependent chaperone that facilitates dissociation of inhibitory sugar phosphates from the catalytic sites of ribulose-1,5-bisphosphate carboxylase/oxygenase during photosynthesis. In Arabidopsis, Rubisco activase is negatively regulated by dark-dependent phosphorylation of threonine 78. The prevalence of threonine 78 in Rubisco activase was investigated across sequences from 91 plant species, finding 29 (∼32%) species shared a threonine in the same position. Analysis of seven C3 species with an antibody raised against a threonine 78 phospho-peptide demonstrated that this position is phosphorylated in multiple genera. However, light-dependent dephosphorylation of threonine 78 was observed only in Arabidopsis. Further, phosphorylation of threonine 78 could not be detected in any of the four C4 grass species examined. The results suggest that despite conservation of threonine 78 in Rubisco activase from a wide range of species, a regulatory role for phosphorylation at this site is more limited. This provides a case study for how variation in post-translational regulation can amplify functional divergence across the phylogeny of plants beyond what is explained by sequence variation in a metabolically important protein.
Beyond bacterial paradigms: uncovering the functional significance and first biogenesis machinery of archaeal lipoproteins
Authors: Hong Yirui , Makarova Kira S. , Xu Rachel , Pfeiffer Friedhelm , Pohlschroder Mechthild 
Published: August 2024

AbstractLipoproteins are major constituents of prokaryotic cell surfaces. In bacteria, lipoprotein attachment to membrane lipids is catalyzed by prolipoprotein diacylglyceryl transferase (Lgt). However, no Lgt homologs have been identified in archaea, suggesting the unique archaeal membrane lipids require distinct enzymes for lipoprotein lipidation. Here, we performedin silicopredictions for all major archaeal lineages and revealed a high prevalence of lipoproteins across the domain Archaea. Using comparative genomics, we identified the first set of candidates for archaeal lipoprotein biogenesis components (Ali). Genetic and biochemical characterization confirmed two paralogous genes,aliAandaliB, are important for lipoprotein lipidation in the archaeonHaloferax volcanii. Disruption of AliA- and AliB-mediated lipoprotein lipidation results in severe growth defects, decreased motility, and cell-shape alterations, underscoring the importance of lipoproteins in archaeal cell physiology. AliA and AliB also exhibit different enzymatic activities, including potential substrate selectivity, uncovering a new layer of regulation for prokaryotic lipoprotein lipidation.
Temporally discordant chromatin accessibility and DNA demethylation define short and long-term enhancer regulation during cell fate specification
Authors: Guerin Lindsey N. , Scott Timothy J. , Yap Jacqueline A. , Johansson Annelie , Puddu Fabio , Charlesworth Tom , Yang Yilin , Simmons Alan J. , Lau Ken S. , Ihrie Rebecca A. , Hodges Emily 
Published: August 2024

SUMMARYEpigenetic mechanisms govern the transcriptional activity of lineage-specifying enhancers; but recent work challenges the dogma that joint chromatin accessibility and DNA demethylation are prerequisites for transcription. To understand this paradox, we established a highly-resolved timeline of DNA demethylation, chromatin accessibility, and transcription factor occupancy during neural progenitor cell differentiation. We show thousands of enhancers undergo rapid, transient accessibility changes associated with distinct periods of transcription factor expression. However, most DNA methylation changes are unidirectional and delayed relative to chromatin dynamics, creating transiently discordant epigenetic states. Genome-wide detection of 5-hydroxymethylcytosine further revealed active demethylation begins ahead of chromatin and transcription factor activity, while enhancer hypomethylation persists long after these activities have dissipated. We demonstrate that these timepoint specific methylation states predict past, present and future chromatin accessibility using machine learning models. Thus, chromatin and DNA methylation collaborate on different timescales to mediate short and long-term enhancer regulation during cell fate specification.
Machine learning and data-driven inverse modeling of metabolomics unveil key process of active aging
Authors: Li Jiahang , Brenner Martin , Pierides Iro , Wessner Barbara , Franzke Bernhard , Strasser Eva-Maria , Waldherr Steffen , Wagner Karl-Heinz , Weckwerth Wolfram 
Published: August 2024

AbstractPhysical inactivity and a weak fitness status have become a global health concern. Metabolomics, as an integrative systematic approach, might link to individual’s fitness at the molecular level. In this study, we performed blood samples metabolomics analysis of a cohort of elderly people with different treatments. By defining two groups of fitness and corresponding metabolites profiles, we tested several machine learning classification approaches to identify key metabolite biomarkers, which showed robustly aspartate as a dominant negative marker of fitness. Following, the metabolomics data of the two groups were analyzed by a novel approach for metabolic network interaction termed COVRECON. Where we identified the enzyme AST as the most important metabolic regulation between the fit and the less fit groups. Routine blood tests in these two cohorts validated significant differences in AST and ALT. In summary, we combine machine learning classification and COVRECON to identify metabolomics biomarkers and causal processes for fitness of elderly people.
Yes, they’re all individuals: Hierarchical models from repeat measurement data improve estimates of tree growth and size
Authors: O’Brien Theresa , Warton David , Falster Daniel 
Published: August 2024

AbstractRepeat measurement surveys of tree size are used in forests to estimate growth be-haviour, biomass, and population dynamics. Although size is measured with error, and individuals vary in their growth trajectories, current size-based growth modelling approaches do not usually or fully account for both of these features, and therefore under-utilise available data.We present a new method that leverages the auto-correlation structure of repeat surveys into a hierarchical Bayesian longitudinal growth model. This new structure allows users to correct for measurement error and capture individual-level variation in growth trajectories and parameters.To demonstrate the new method we applied it to a sample of tropical tree survey data from long-term monitoring sites at Barro Colorado Island. We were able to reduce estimated error in size and growth, and extract individual-and population-level growth parameter estimates. We used simulation to evaluate the ability of the new method to improve estimates of growth rate and size, and estimate individual and species-level parameters. Our method substantially improved RMSE for growth by an average of 61% compared to existing approaches using pairwise differences; and reduced RMSE in estimated size RMSE compared to ‘observed’ values in simulated data. Better numerical integration methods (Runge-Kutta 4th order in comparison to Euler and midpoint) provided better estimates of parameters, but did not improve the estimation of size and growth. The choice of a positive growth function eliminated all negative increments without data exclusion.Overall, this study shows how we can gain new and improved insights on growth, using repeat forest surveys. Our new method offers improved biomass dynamics estimation through reduced error in sizes over time, coupled with novel information about within-species variation in growth behaviour that is inaccessible with species average models, such as individual parameters for the growth function which allows for relationships between parameters to be considered for the first time.
Time-resolved, integrated multi-omic analysis reveals central role of amino acid pathways for defense responses inArabidopsis thaliana
Authors: Joller Charlotte , Schläppi Klaus , Sasse Joelle 
Published: August 2024

AbstractPlants respond to biotic stresses by altering gene expression and metabolism. However, how fast different tissues respond to microbial presence, and how similar these responses are is mostly unresolved. Here, we treatArabidopsis thalianawith elicitors and investigate time-resolved changes in shoot, root, and root-derived (exudate) metabolite profiles. We find that root responses precede shoots and that first metabolite changes take place after 1.5 h and persist for 3 d. Exudates respond within 4 h (earliest timepoint available) to elicitor presence. This response diminishes when plants are pulse-treated but persists for continuously treated plants. Defense compounds such as phenylpropanoids increase after 1.5-4 h. Amino acids were iden6fied as central players in defense: they increase after 1.5 h in shoots, roots, and exudates. Transcriptome analysis at 4 h and 1 d and integrated, multi-omic analysis of transcription and metabolome suggest that aromatic and aliphatic amino acids are central players in defense responses. As their transcriptional and metabolite increases are fast and persisting over days for most amino acids, we propose amino acids as early indicators for biotic stress monitoring.
Comparative transcriptomics in ferns reveals key innovations and divergent evolution of the secondary cell walls
Authors: Ali Zahin Mohd , Tan Qiao Wen , Lim Peng Ken , Chen Hengchi , Pfeifer Lukas , Julca Irene , Lee Jia Min , Classen Birgit , Vries Sophie de , Vries Jan de , Koh Teng Seah , Chin Li Li , Vinter Fanny , Alvarado Camille , Layens Amandine , Mizrachi Eshchar , Motawie Mohammed Saddik , Joergensen Bodil , Ulvskov Peter , de Peer Yves van , Ho Boon Chuan , Sibout Richard , Mutwil Marek 
Published: August 2024

AbstractDespite ferns being crucial to understanding plant evolution, their large and complex genomes has kept their genetic landscape largely uncharted, with only a handful of genomes sequenced and sparse transcriptomic data. Addressing this gap, we generated extensive RNA-sequencing data for multiple organs across 22 representative species over the fern phylogeny, assembling high-quality transcriptomes. These data facilitated the construction of a time-calibrated fern phylogeny covering all major clades, revealing numerous whole-genome duplications and highlighting the uniqueness of fern genetics, with half of the uncovered gene families being fern-specific. Our investigation into fern cell walls through biochemical and immunological analyses identified occurrences of the lignin syringyl unit and its independent evolution in ferns. Moreover, the discovery of an unusual sugar in fern cell walls hints at a divergent evolutionary path in cell wall biochemistry, potentially driven by gene duplication and sub-functionalization. We provide an online database preloaded with genomic and transcriptomic data for ferns and other land plants, which we used to identify an independent evolution of lignocellulosic gene modules in ferns. Our data provide a framework for the unique evolutionary path that ferns have navigated since they split from the last common ancestor of euphyllophytes more than 360 million years ago.
Near-infrared MINFLUX imaging enabled by suppression of fluorophore blinking
Authors: Srambickal C Venugopal , Esmaeeli H , Piguet J , Reinkensmeier L , Siegmund R , Bates M , Egner A , Widengren J 
Published: August 2024

AbstractMINimal photon FLUXes (MINFLUX) offers super-resolution microscopy (SRM) with nanometer localization precision, with more relaxed fluorophore brightness and photostability requirements than for other SRM techniques. Nonetheless, low localization probabilities have been reported in several MINFLUX studies, and a broader use of less bright and photostable fluorophores, including near-infrared (NIR) fluorophores has been difficult to realize. In this work, we identified fluorophore blinking as a main cause of erroneous (and dismissed) fluorophore localizations in MINFLUX imaging and devised strategies to overcome these effects. We systematically studied the blinking/switching properties of cyanine fluorophores emitting in the far-red or NIR range, and over typical time scales (µs-10ms), sample and excitation conditions used in MINFLUX imaging. By subsequent simulations of representative MINFLUX localization procedures, we found that trans-cis isomerization, and in particular photo-reduction of the fluorophores, can generate significant localization errors. However, these localization errors could be suppressed by balanced redox buffers and repetitive excitation beam scans. Implementing these strategies, and replacing the slower, intrinsic switching of the fluorophores needed for the localization by transient binding of fluorophore-labelled DNA strands to complementary DNA strands attached to the targets (DNA-PAINT), we could for the first time demonstrate NIR-MINFLUX imaging with nanometer localization precision. This work presents an overall strategy, where fluorophore blinking characterization and subsequent simulations make it possible to design optimal sample and excitation conditions, opening for NIR-MINFLUX imaging, as well as for a broader use of fluorophores in MINFLUX and related SRM studies.