bluuebunny/crossref_metadata_2025_split huggingface dataset:
Representation and Reality in Kant’s Antinomy of Pure Reason
Authors: Melamedoff-Vosters Damian 
Published: October 2023

AbstractIn this article, I take on a classic objection to Kant’s arguments in the Antinomy of Pure Reason: that the arguments are question-begging, as they draw illicit inferences from claims about representation to claims about reality. While extant attempts to vindicate Kant try to show that he does not make such inferences, I attempt to vindicate Kant’s arguments in a different way: I show that, given Kant’s philosophical backdrop, the inferences in question are not illicit. This is because the transcendental realists that Kant was arguing against have certain philosophical commitments about the nature of ground which, if true, warrant the inferences that Kant draws. This historical corrective not only allows us to better understand Kant’s own thinking in the Antinomies but it also has important upshots for our understanding of Kant’s transcendental idealism.
Intertwined maritime Silk Road and Austronesian routes: A Taiwanese archaeological perspective
Authors: Liu Jiun-Yu 
Published: October 2023

AbstractThis article analyses recent archaeological work on the flow of materials and their influences on the communities in the South China Sea maritime regions, primarily from a local, Taiwanese perspective. The intertwined Austronesian Routes and maritime Silk Road acted as the primary conduit for the movement of both people and materials. Archaeological findings demonstrate intermittent interaction and cultural exchange between Taiwan and the regions around the South China Sea during the period 1,500-500 BCE. However, starting from 500 BCE, the gradual increase of glass beads, agate beads, and metal products which were made in mainland Southeast Asia and adjacent regions indicate an intensified interaction between Taiwan and Southeast Asia via the Maritime Silk Road and the Austronesian Routes. The author hypothesizes that trade diasporic craftspeople were the carriers of these exotic materials and knowledge, and that external cultural elements had a profound impact on the development of contemporary prehistoric Formosan society. This can be seen most notably in the shifting of decoration systems, the changing methods of subsistence, and technological leaps. Some of the impacts have faded into the archaeological records, but others are still traceable in the modern Indigenous society of Taiwan.
High intensity perturbations induce an abrupt shift in soil microbial state
Authors: Cordero Irene , Leizeaga Ainara , Hicks Lettice C , Rousk Johannes , Bardgett Richard D 
Published: October 2023

Abstract
Soil microbial communities play a pivotal role in regulating ecosystem functioning. But they are increasingly being shaped by human-induced environmental change, including intense “pulse” perturbations, such as droughts, which are predicted to increase in frequency and intensity with climate change. While it is known that soil microbial communities are sensitive to such perturbations and that effects can be long-lasting, it remains untested whether there is a threshold in the intensity and frequency of perturbations that can trigger abrupt and persistent transitions in the taxonomic and functional characteristics of soil microbial communities. Here we demonstrate experimentally that intense pulses of drought equivalent to a 30-year drought event (&lt;15% WHC) induce a major shift in the soil microbial community characterised by significantly altered bacterial and fungal community structures of reduced complexity and functionality. Moreover, the characteristics of this transformed microbial community persisted after returning soil to its previous moisture status. As a result, we found that drought had a strong legacy effect on bacterial community function, inducing an enhanced growth rate following subsequent drought. Abrupt transitions are widely documented in aquatic and terrestrial plant communities in response to human-induced perturbations. Our findings demonstrate that such transitions also occur in soil microbial communities in response to high intensity pulse perturbations, with potentially deleterious consequences for soil health.
Population genomic diversity and structure in the golden bandicoot: a history of isolation, extirpation, and conservation
Authors: Rick Kate , Byrne Margaret , Cameron Skye , Cooper Steve J. B. , Dunlop Judy , Hill Brydie , Lohr Cheryl , Mitchell Nicola J. , Moritz Craig , Travouillon Kenny J. , von Takach Brenton , Ottewell Kym 
Published: October 2023

AbstractUsing genetic information to develop and implement conservation programs is vital for maintaining biodiversity and ecosystem resilience. Evaluation of the genetic variability within and among remnant populations can inform management of both natural and translocated populations to maximise species’ adaptive potential, mitigate negative impacts of inbreeding, and subsequently minimise risk of extinction. Here we use reduced representation sequencing to undertake a genetic assessment of the golden bandicoot (Isoodon auratus), a threatened marsupial endemic to Australia. The currently recognised taxon consists of three subspecies distributed among multiple natural and translocated populations. After confirming the genetic distinctiveness of I. auratus from two closely related taxa, I. fusciventer and I. macrourus, we identified four genetic clusters within I. auratus. These clusters exhibited substantial genetic differentiation (pairwise FST values ranging from 0.18 to 0.65, pairwise DXY ranging from 0.1 to 0.168), reflecting long-term isolation of some populations on offshore islands and the influence of genetic drift. Mainland natural populations in the Kimberley region had the highest genetic diversity and the largest contribution to overall allelic and gene diversity compared to both natural and translocated island populations. A population translocated to Guluwuru Island in the Northern Territory had the lowest genetic diversity. Our data suggest that island populations can appear genetically unique due to genetic drift and this needs to be taken into account when considering genetic diversity in conservation efforts to maintain overall genetic diversity of the species. We effectively demonstrate how genomic information can guide practical conservation planning, especially when declining species are represented by multiple isolated populations.
Over 200,000 kilometers of free-flowing river habitat in Europe is altered due to impoundments
Authors: Parasiewicz Piotr , Belka Kamila , Łapińska Małgorzata , Ławniczak Karol , Prus Paweł , Adamczyk Mikołaj , Buras Paweł , Szlakowski Jacek , Kaczkowski Zbigniew , Krauze Kinga , O’Keeffe Joanna , Suska Katarzyna , Ligięza Janusz , Melcher Andreas , O’Hanley Jesse , Birnie-Gauvin Kim , Aarestrup Kim , Jones Peter E. , Jones Joshua , Garcia de Leaniz Carlos , Tummers Jeroen S. , Consuegra Sofia , Kemp Paul , Schwedhelm Hannah , Popek Zbigniew , Segura Gilles , Vallesi Sergio , Zalewski Maciej , Wiśniewolski Wiesław 
Published: October 2023

AbstractEuropean rivers are disconnected by more than one million man-made barriers that physically limit aquatic species migration and contribute to modification of freshwater habitats. Here, a Conceptual Habitat Alteration Model for Ponding is developed to aid in evaluating the effects of impoundments on fish habitats. Fish communities present in rivers with low human impact and their broad environmental settings enable classification of European rivers into 15 macrohabitat types. These classifications, together with the estimated fish sensitivity to alteration of their habitat are used for assessing the impacts of six main barrier types (dams, weirs, sluices, culverts, fords, and ramps). Our results indicate that over 200,000 km or 10% of previously free-flowing river habitat has been altered due to impoundments. Although they appear less frequently, dams, weirs and sluices cause much more habitat alteration than the other types. Their impact is regionally diverse, which is a function of barrier height, type and density, as well as biogeographical location. This work allows us to foresee what potential environmental gain or loss can be expected with planned barrier management actions in rivers, and to prioritize management actions.
Regulation of CTCF loop formation during pancreatic cell differentiation
Authors: Lyu Xiaowen , Rowley M. Jordan , Kulik Michael J. , Dalton Stephen , Corces Victor G. 
Published: October 2023

AbstractTranscription reprogramming during cell differentiation involves targeting enhancers to genes responsible for establishment of cell fates. To understand the contribution of CTCF-mediated chromatin organization to cell lineage commitment, we analyzed 3D chromatin architecture during the differentiation of human embryonic stem cells into pancreatic islet organoids. We find that CTCF loops are formed and disassembled at different stages of the differentiation process by either recruitment of CTCF to new anchor sites or use of pre-existing sites not previously involved in loop formation. Recruitment of CTCF to new sites in the genome involves demethylation of H3K9me3 to H3K9me2, demethylation of DNA, recruitment of pioneer factors, and positioning of nucleosomes flanking the new CTCF sites. Existing CTCF sites not involved in loop formation become functional loop anchors via the establishment of new cohesin loading sites containing NIPBL and YY1 at sites between the new anchors. In both cases, formation of new CTCF loops leads to strengthening of enhancer promoter interactions and increased transcription of genes adjacent to loop anchors. These results suggest an important role for CTCF and cohesin in controlling gene expression during cell differentiation.
A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models
Authors: Wirth Fabian , Heitz Fabrice D. , Seeger Christine , Combaluzier Ioana , Breu Karin , Denroche Heather C. , Thevenet Julien , Osto Melania , Arosio Paolo , Kerr-Conte Julie , Verchere C. Bruce , Pattou François , Lutz Thomas A. , Donath Marc Y. , Hock Christoph , Nitsch Roger M. , Grimm Jan 
Published: October 2023

AbstractIn patients with type 2 diabetes, pancreatic beta cells progressively degenerate and gradually lose their ability to produce insulin and regulate blood glucose. Beta cell dysfunction and loss is associated with an accumulation of aggregated forms of islet amyloid polypeptide (IAPP) consisting of soluble prefibrillar IAPP oligomers as well as insoluble IAPP fibrils in pancreatic islets. Here, we describe a human monoclonal antibody selectively targeting IAPP oligomers and neutralizing IAPP aggregate toxicity by preventing membrane disruption and apoptosis in vitro. Antibody treatment in male rats and mice transgenic for human IAPP, and human islet-engrafted mouse models of type 2 diabetes triggers clearance of IAPP oligomers resulting in beta cell protection and improved glucose control. These results provide new evidence for the pathological role of IAPP oligomers and suggest that antibody-mediated removal of IAPP oligomers could be a pharmaceutical strategy to support beta cell function in type 2 diabetes.
Bone disease imaging through the near-infrared-II window
Authors: Mi Chao , Zhang Xun , Yang Chengyu , Wu Jianqun , Chen Xinxin , Ma Chenguang , Wu Sitong , Yang Zhichao , Qiao Pengzhen , Liu Yang , Wu Weijie , Guo Zhiyong , Liao Jiayan , Zhou Jiajia , Guan Ming , Liang Chao , Liu Chao , Jin Dayong 
Published: October 2023

AbstractSkeletal disorders are commonly diagnosed by X-ray imaging, but the radiation limits its use. Optical imaging through the near-infrared-II window (NIR-II, 1000–1700 nm) can penetrate deep tissues without radiation risk, but the targeting of contrast agent is non-specific. Here, we report that lanthanide-doped nanocrystals can passively target the bone marrow, which can be effective for over two months. We therefore develop the high-resolution NIR-II imaging method for bone disease diagnosis, including the 3D bone imaging instrumentation to show the intravital bone morphology. We demonstrate the monitoring of 1 mm bone defects with spatial resolution comparable to the X-ray imaging result. Moreover, NIR-II imaging can reveal the early onset inflammation as the synovitis in the early stage of rheumatoid arthritis, comparable to micro computed tomography (μCT) in diagnosis of osteoarthritis, including the symptoms of osteophyte and hyperostosis in the knee joint.
Single-cell allele-specific expression analysis reveals dynamic and cell-type-specific regulatory effects
Authors: Qi Guanghao , Strober Benjamin J. , Popp Joshua M. , Keener Rebecca , Ji Hongkai , Battle Alexis 
Published: October 2023

AbstractDifferential allele-specific expression (ASE) is a powerful tool to study context-specific cis-regulation of gene expression. Such effects can reflect the interaction between genetic or epigenetic factors and a measured context or condition. Single-cell RNA sequencing (scRNA-seq) allows the measurement of ASE at individual-cell resolution, but there is a lack of statistical methods to analyze such data. We present Differential Allelic Expression using Single-Cell data (DAESC), a powerful method for differential ASE analysis using scRNA-seq from multiple individuals, with statistical behavior confirmed through simulation. DAESC accounts for non-independence between cells from the same individual and incorporates implicit haplotype phasing. Application to data from 105 induced pluripotent stem cell (iPSC) lines identifies 657 genes dynamically regulated during endoderm differentiation, with enrichment for changes in chromatin state. Application to a type-2 diabetes dataset identifies several differentially regulated genes between patients and controls in pancreatic endocrine cells. DAESC is a powerful method for single-cell ASE analysis and can uncover novel insights on gene regulation.
Multivalent insulin receptor activation using insulin–DNA origami nanostructures
Authors: Spratt Joel , Dias José M. , Kolonelou Christina , Kiriako Georges , Engström Enya , Petrova Ekaterina , Karampelias Christos , Cervenka Igor , Papanicolaou Natali , Lentini Antonio , Reinius Björn , Andersson Olov , Ambrosetti Elena , Ruas Jorge L. , Teixeira Ana I. 
Published: October 2023

AbstractInsulin binds the insulin receptor (IR) and regulates anabolic processes in target tissues. Impaired IR signalling is associated with multiple diseases, including diabetes, cancer and neurodegenerative disorders. IRs have been reported to form nanoclusters at the cell membrane in several cell types, even in the absence of insulin binding. Here we exploit the nanoscale spatial organization of the IR to achieve controlled multivalent receptor activation. To control insulin nanoscale spatial organization and valency, we developed rod-like insulin–DNA origami nanostructures carrying different numbers of insulin molecules with defined spacings. Increasing the insulin valency per nanostructure markedly extended the residence time of insulin–DNA origami nanostructures at the receptors. Both insulin valency and spacing affected the levels of IR activation in adipocytes. Moreover, the multivalent insulin design associated with the highest levels of IR activation also induced insulin-mediated transcriptional responses more effectively than the corresponding monovalent insulin nanostructures. In an in vivo zebrafish model of diabetes, treatment with multivalent—but not monovalent—insulin nanostructures elicited a reduction in glucose levels. Our results show that the control of insulin multivalency and spatial organization with nanoscale precision modulates the IR responses, independent of the insulin concentration. Therefore, we propose insulin nanoscale organization as a design parameter in developing new insulin therapies.
Chiral and nematic phases of flexible active filaments
Authors: Dunajova Zuzana , Mateu Batirtze Prats , Radler Philipp , Lim Keesiang , Brandis Dörte , Velicky Philipp , Danzl Johann Georg , Wong Richard W. , Elgeti Jens , Hannezo Edouard , Loose Martin 
Published: October 2023

AbstractThe emergence of large-scale order in self-organized systems relies on local interactions between individual components. During bacterial cell division, FtsZ—a prokaryotic homologue of the eukaryotic protein tubulin—polymerizes into treadmilling filaments that further organize into a cytoskeletal ring. In vitro, FtsZ filaments can form dynamic chiral assemblies. However, how the active and passive properties of individual filaments relate to these large-scale self-organized structures remains poorly understood. Here we connect single-filament properties with the mesoscopic scale by combining minimal active matter simulations and biochemical reconstitution experiments. We show that the density and flexibility of active chiral filaments define their global order. At intermediate densities, curved, flexible filaments organize into chiral rings and polar bands. An effectively nematic organization dominates for high densities and for straight, mutant filaments with increased rigidity. Our predicted phase diagram quantitatively captures these features, demonstrating how the flexibility, density and chirality of the active filaments affect their collective behaviour. Our findings shed light on the fundamental properties of active chiral matter and explain how treadmilling FtsZ filaments organize during bacterial cell division.
Age-dependent topic modeling of comorbidities in UK Biobank identifies disease subtypes with differential genetic risk
Authors: Jiang Xilin , Zhang Martin Jinye , Zhang Yidong , Durvasula Arun , Inouye Michael , Holmes Chris , Price Alkes L. , McVean Gil 
Published: October 2023

AbstractThe analysis of longitudinal data from electronic health records (EHRs) has the potential to improve clinical diagnoses and enable personalized medicine, motivating efforts to identify disease subtypes from patient comorbidity information. Here we introduce an age-dependent topic modeling (ATM) method that provides a low-rank representation of longitudinal records of hundreds of distinct diseases in large EHR datasets. We applied ATM to 282,957 UK Biobank samples, identifying 52 diseases with heterogeneous comorbidity profiles; analyses of 211,908 All of Us samples produced concordant results. We defined subtypes of the 52 heterogeneous diseases based on their comorbidity profiles and compared genetic risk across disease subtypes using polygenic risk scores (PRSs), identifying 18 disease subtypes whose PRS differed significantly from other subtypes of the same disease. We further identified specific genetic variants with subtype-dependent effects on disease risk. In conclusion, ATM identifies disease subtypes with differential genome-wide and locus-specific genetic risk profiles.
Population-level integration of single-cell datasets enables multi-scale analysis across samples
Authors: De Donno Carlo , Hediyeh-Zadeh Soroor , Moinfar Amir Ali , Wagenstetter Marco , Zappia Luke , Lotfollahi Mohammad , Theis Fabian J. 
Published: October 2023

AbstractThe increasing generation of population-level single-cell atlases has the potential to link sample metadata with cellular data. Constructing such references requires integration of heterogeneous cohorts with varying metadata. Here we present single-cell population level integration (scPoli), an open-world learner that incorporates generative models to learn sample and cell representations for data integration, label transfer and reference mapping. We applied scPoli on population-level atlases of lung and peripheral blood mononuclear cells, the latter consisting of 7.8 million cells across 2,375 samples. We demonstrate that scPoli can explain sample-level biological and technical variations using sample embeddings revealing genes associated with batch effects and biological effects. scPoli is further applicable to single-cell sequencing assay for transposase-accessible chromatin and cross-species datasets, offering insights into chromatin accessibility and comparative genomics. We envision scPoli becoming an important tool for population-level single-cell data integration facilitating atlas use but also interpretation by means of multi-scale analyses.
Compact engineered human mechanosensitive transactivation modules enable potent and versatile synthetic transcriptional control
Authors: Mahata Barun , Cabrera Alan , Brenner Daniel A. , Guerra-Resendez Rosa Selenia , Li Jing , Goell Jacob , Wang Kaiyuan , Guo Yannie , Escobar Mario , Parthasarathy Abinand Krishna , Szadowski Hailey , Bedford Guy , Reed Daniel R. , Kim Sunghwan , Hilton Isaac B. 
Published: October 2023

AbstractEngineered transactivation domains (TADs) combined with programmable DNA binding platforms have revolutionized synthetic transcriptional control. Despite recent progress in programmable CRISPR–Cas-based transactivation (CRISPRa) technologies, the TADs used in these systems often contain poorly tolerated elements and/or are prohibitively large for many applications. Here, we defined and optimized minimal TADs built from human mechanosensitive transcription factors. We used these components to construct potent and compact multipartite transactivation modules (MSN, NMS and eN3x9) and to build the CRISPR–dCas9 recruited enhanced activation module (CRISPR-DREAM) platform. We found that CRISPR-DREAM was specific and robust across mammalian cell types, and efficiently stimulated transcription from diverse regulatory loci. We also showed that MSN and NMS were portable across Type I, II and V CRISPR systems, transcription activator-like effectors and zinc finger proteins. Further, as proofs of concept, we used dCas9-NMS to efficiently reprogram human fibroblasts into induced pluripotent stem cells and demonstrated that mechanosensitive transcription factor TADs are efficacious and well tolerated in therapeutically important primary human cell types. Finally, we leveraged the compact and potent features of these engineered TADs to build dual and all-in-one CRISPRa AAV systems. Altogether, these compact human TADs, fusion modules and delivery architectures should be valuable for synthetic transcriptional control in biomedical applications.
An evaluation tool for backbone extraction techniques in weighted complex networks
Authors: Yassin Ali , Haidar Abbas , Cherifi Hocine , Seba Hamida , Togni Olivier 
Published: October 2023

AbstractNetworks are essential for analyzing complex systems. However, their growing size necessitates backbone extraction techniques aimed at reducing their size while retaining critical features. In practice, selecting, implementing, and evaluating the most suitable backbone extraction method may be challenging. This paper introduces , a Python package designed for assessing the performance of backbone extraction techniques in weighted networks. Its comparison framework is the standout feature of . Indeed, the tool incorporates state-of-the-art backbone extraction techniques. Furthermore, it provides a comprehensive suite of evaluation metrics allowing users to evaluate different backbones techniques. We illustrate the flexibility and effectiveness of through the US air transportation network analysis. We compare the performance of different backbone extraction techniques using the evaluation metrics. We also show how users can integrate a new backbone extraction method into the comparison framework. is publicly available as an open-source tool, ensuring its accessibility to researchers and practitioners. Promoting standardized evaluation practices contributes to the advancement of backbone extraction techniques and fosters reproducibility and comparability in research efforts. We anticipate that will serve as a valuable resource for researchers and practitioners enabling them to make informed decisions when selecting backbone extraction techniques to gain insights into the structural and functional properties of complex systems.