bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mendelian randomization suggests a causal link between glycemic traits and thoracic aortic structures and diseases
Authors: Daria Tselmen , Iyer Kruthika , Alkhairo Hasan , Fang Kho Pik , Suzuki Ken , Hatzikotoulas Konstantinos , Southam Lorraine , Taylor Henry J , Yin Xianyong , Mandla Ravi , Huerta-Chagoya Alicia , Rayner Nigel W , Levin Michael G. , Damrauer Scott M , Tsao Philip S , Priest James R , Pirruccello James , Echouffo Tcheugui Justin B , Tcheandjieu Catherine 
Published: September 2024

AbstractImportanceType 2 diabetes mellitus (T2DM) and elevated glucose levels have been inversely associated with aortic aneurysms. However, the causality of this relationship remains uncertain. Additionally, there is a lack of studies investigating the association between glycemic traits and imaging-based thoracic aortic phenotypes.ObjectiveWe investigated whether T2DM and glycemic measures (fasting glucose (FG), fasting insulin (FI), glycated hemoglobin (HbA1c), and 2-hour post-load glucose (2hPG)) are causally associated with various imaging and clinical thoracic aortic phenotypes.Design, setting, and participantsWe performed Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies of glycemic traits (GT) and aortic phenotypes. We employed a two-sample univariate MR (UVMR) followed by a multivariable MR and MR analysis using a cluster-based approach.Main Outcomes and MeasuresThe outcome includes imaging-based ascending and descending aortic diameters (AAoD and DAoD), aortic distensibility (AoDist) and strain (AoStr), and thoracic aortic aneurysm and dissection (TAAD). The GT include FI, FG, HbA1c, 2hPG and T2DM.ResultsWe observed an inverse association between 2hPG, FG, HbA1c, and T2DM and AAoD, DAoD. For instance, the genetically predicted increases levels of 2hPG, FG, HbA1c, and T2DM were associated with decreased AAoD (2hPG β= -0.2, p=3x10-08; FG β= -0.21, p=5x10-05; HbA1c β= -0.36, p=2x10-07; T2DM β=-0.04, p=2x10-04) and reduce risk TAAD (2hPG decreased TAAD (2hPG OR= 0.70, p=4x10-04; FG OR= 0.58, p=3x10-05; HbA1c OR= 0.62, p=5x10-03; T2DM OR= 0.90, p=6x10-6). Further investigation showed that the inverse association between T2DM and aortic phenotypes is driven by genetic predictors of T2DM beta cell proinsulin clusters. UVMR and Proteomic MR showed a strong association with aortic phenotypes for genes, suchas AGER, GLRX, TCF7L2, andGCK, which are known to play an important role in glucose regulation.Conclusion and relevanceOur findings suggest a potentially causal impact of GT on the aortic vasculature. Furthermore, specific glucose regulation genes such asGCK,AGER, andTCF7L2appear to contribute to this process, opening avenues for potentially leveraging the druggability of these genes for treatment or preventions of TAAD.
Health Data Reporting Challenges in the Age of DHIS2: a Mixed-Methods Review in the Teso Sub-Region of Uganda
Authors: Lawrence Margaret R. , Fuller Benjamin P. , Isabirye Herbert Kirya , Kyozira Carol , Makumbi Issa , Bakainaga Andrew , Moore Christopher C. , Ssekitoleko Richard 
Published: September 2024

ABSTRACTIn Uganda, the complete and timely reporting of priority disease data by health centers is critical for detecting outbreaks. However, health centers face significant reporting challenges, which compromise data fidelity and public health. To assess the efficacy of existing systems, we aimed to (1) compare reporting performance among districts in the Teso region of Eastern Uganda, (2) ascertain the association between volume of outpatient department (OPD) visits and reporting rates at facilities, and (3) characterize reporting challenges. We queried Uganda’s Electronic Health Management Information System database, DHIS2, regarding the completeness (reporting rate) and timeliness (reporting rate on time) of priority disease data submission within Teso from January-April 2024. We selected the 3 lowest-performing districts in both metrics and assessed reporting at all health centers within these districts. We used linear regression to determine the relationship between the aggregate number of outpatient visits per health facility and their mean reporting rates. At 7 health facilities across the 3 districts, we interviewed staff to enumerate reporting challenges. Of all 11 districts in Teso, 7 (64%) scored >80% for completeness and 2 (18%) scored >80% for submission timeliness across health facilities. The median (IQR) scores for completeness and timeliness were 83% (75-93%) and 69% (55-75%), respectively. The 3 lowest performing districts in both metrics were Soroti City, Soroti district, and Ngora district. In Soroti City, increasing number of OPD visits was associated with higher reporting rate percentages (b [slope]=0.005, p=0.01). The main reasons given for low reporting rates included limited staff trained on data entry protocols, competing responsibilities among reporting personnel, and lack of reliable internet access. The implementation of DHIS2 has improved public health and disease surveillance in Uganda, but institutional-level data reporting challenges continue to impair disease tracking. Targeted interventions to relieve such barriers is possible.
Droplet Sequencing Reveals Virulence Gene Clusters in Oral Biofilm Extracellular Vesicles
Authors: Takano Sotaro , Divya Naradasu , Takenawa Satoshi , Kangmin Yan , Maehara Tomoko , Nomura Nobuhiko , Obana Nozomu , Toyofuku Masanori , Usui Michihiko , Ariyoshi Wataru , Okamoto Akihiro 
Published: September 2024

AbstractBacterial extracellular vesicles (BEVs), produced by a broad spectrum of bacteria, play a crucial role in enhancing intercellular communication through DNA transfer. A vital determinant of their gene transfer efficiency is the gene content diversity within BEVs, an aspect that conventional metagenomics fails to capture. Our study bridges this gap with a novel microdroplet-based sequencing technique that precisely details DNA content within hundreds of individual BEVs. This technique revealed a unique DNA profile in BEVs from the oral pathogenPorphyromonas gingivalis, pinpointing specific genomic regions related to DNA integration (e.g., DNA transposition and CRISPR-Cas systems). These enriched genes, overlooked by standard analyses that aggregate total read counts, indicate that our method offers a more focused view into the genetic contents of BEVs. Applying our technique to dental plaque-derived BEVs, we discovered a hundredfold higher prevalence of DNA encapsulation than previously estimated, with over 30% of BEVs containing DNA. Specifically, we identified a substantial presence of O-antigen biosynthesis genes, prominent hotspots of frequent horizontal gene transfer, fromAlcaligenes faecalis. Given that O-antigens mediate host-bacterial interactions, this gene enrichment in the large fraction of BEVs suggests a potential novel pathway by which BEVs could influence pathogenicity within oral biofilms. Our research unveils critical insights into the potential functions of vesicular DNA in microbial communities, establishing a powerful platform for studying vesicular DNA in microbiomes. This technical breakthrough provides a foundational basis for future research in microbial communication and the development of potential therapeutic or diagnosis strategies.Significance StatementBEVs have been studied for decades, yet their roles in nature and disease are just beginning to be appreciated. Our study makes a significant leap in understanding the roles of BEVs as gene transfer vehicles. By developing a microdroplet-based sequencing technique, we have uncovered detailed DNA profiles within individual BEVs, a task beyond the capabilities of conventional metagenomic methods. This breakthrough highlights specific genomic regions enriched in BEVs from pure culture and human dental plaque. Furthermore, the high prevalence of biofilm BEVs enriched in O-antigen biosynthesis genes, suggests a potential impact on the pathogenicity of oral biofilms. This research establishes a new methodological platform for exploring the intricacies of BEV-mediated interactions in a complex microbial community.
SENP2-based N-terminal truncation of α-synuclein in Lewy pathology propagation
Authors: Taguchi Katsutoshi , Watanabe Yoshihisa , Tanaka Masaki 
Published: September 2024

Summaryα-Synuclein (αSyn) is a major component of Lewy bodies (LBs) and Lewy neurites (LNs) which are pathological features of Parkinson’s disease (PD) and Dementia with Lewy bodies. In the PD brain, with disease progression, LB/LN formation is propagated from the lower brainstem to the cerebral cortex. Prion-like cell-to-cell seed-transmission has been implicated as an underlying mechanism for Lewy-pathology propagation. However, the biochemical properties and production mechanism of those pathogenic seeds are unelucidated. In this study, we ascertained that the seeds released from pathological neurons that harbour LB/LN-like aggregates have the N-terminally truncated form of αSyn. This N-terminal truncation is directly catalysed by SENP2, which is a well-known deSUMOylation enzyme. After SENP2 processing of recombinant αSyn, the SDS-resistant high-molecular oligomer formation was promotedin vitro. Inhibition of SENP2 activity suppressed aggregate formation and propagation in cultured neurons and mouse brains. Thus, SENP2 might be a novel therapeutic target in LB diseases.
Joint operation of the CO2concentrating mechanism and photorespiration in green algae during acclimation to limiting CO2
Authors: Dao Ousmane , Bertrand Marie , Alseekh Saleh , Veillet Florian , Auroy Pascaline , Nguyen Phuong-Chi , Légeret Bertrand , Epting Virginie , Morin Amélie , Cuiné Stephan , Monteil Caroline , Mackinder Luke C.M. , Burlacot Adrien , Krieger-Liszkay Anja , Weber Andreas P.M. , Fernie Alisdair R. , Peltier Gilles , Li-Beisson Yonghua 
Published: September 2024

AbstractDue to low availability of CO2in aquatic environment, microalgae have evolved a CO2concentrating mechanism (CCM). It has long been thought that operation of CCM would suppress photorespiration by increasing the CO2concentration at the Rubisco active site, but experimental evidence is scarce. To better explore the function of photorespiration in algae, we first characterized aChlamydomonas reinhardtiimutant defected in low-CO2inducible 20 (LCI20) and show that LCI20 is a chloroplast-envelope glutamate/malate transporter playing a role in photorespiration. By monitoring growth and glycolate excretion in mutants deficient in either CCM or photorespiration, we conclude that:i. CCM induction does not depend on photorespiration,ii. glycolate excretion protects algal cells from the toxicity of unmetabolized photorespiratory intermediates,iii. photorespiration is active at low CO2when the CCM is operational. This work provides a foundation for a better understanding of the carbon cycle in the ocean where significant glycolate concentrations have been found.
Genomic imprinting in an early-diverging angiosperm reveals ancient mechanisms for seed initiation in flowering plants
Authors: Florez-Rueda Ana M. , Scharmann Mathias , de Souza Leonardo P. , Fernie Alisdair R. , Bachelier Julien B. , Figueiredo Duarte D. 
Published: September 2024

AbstractThe evolution of the seed habit marks a pivotal innovation of the spermatophytes. Angiosperms further refined this trait by coupling the development of seed accessory structures to fertilization, optimizing resource allocation. Here, we demonstrate that post-fertilization auxin production is an evolutionarily conserved mechanism for seed initiation in angiosperms. We also provide evidence that this pathway likely emerged from a switch from maternal to paternal control after the divergence of angiosperms from their gymnosperm ancestors. Our study thus brings new insights into the evolutionary origins of the endosperm, which was a determining feature for the rapid rise to dominance of flowering plants.
Deleting PTEN, but not SOCS3 or myelin inhibitors, robustly boosts BRAF-elicited intraspinal regeneration of peripheral sensory axons
Authors: Kim Hyukmin , Noristani Harun N. , Zhai Jinbin , Manire Meredith , Zhai Jinbin , Li Shuxin , Zhong Jian , Son Young-Jin 
Published: September 2024

ABSTRACTPrimary sensory axons fail to regenerate into the spinal cord following dorsal root injury leading to permanent sensory deficits. Re-entry is prevented at the dorsal root entry zone (DREZ), the CNS-PNS interface. Current approaches for promoting DR regeneration across the DREZ have had some success, but sustained, long-distance regeneration, particularly of large-diameter myelinated axons, still remains a formidable challenge. We have previously shown that induced expression of constitutively active B-RAF (kaBRAF) enhanced the regenerative competence of injured DRG neurons in adult mice. In this study, we investigated whether robust intraspinal regeneration can be achieved after a cervical DR injury by selective expression of kaBRAF alone or in combination with deletion of the myelin-associated inhibitors or neuron-intrinsic growth suppressors (PTEN or SOCS3). We found that kaBRAF promoted some axon regeneration across the DREZ but did not produce significant functional recovery by two months. Supplementary deletion of Nogo, MAG, and OMgp only modestly improved kaBRAF-induced regeneration. Deletion of PTEN or SOCS3 individually or in combination failed to promote any growth across the DREZ. In marked contrast, simultaneous deletion of PTEN, but not SOCS3, dramatically enhanced kaBRAF-mediated regeneration enabling many more axons to penetrate the DREZ and grow deep into the spinal cord. This study shows that dual activation of BRAF-MEK-ERK and PI3K-Akt-mTOR signaling is an effective strategy to stimulate robust intraspinal DR regeneration.
Non-cell-autonomous control of gastruloid development by the lncRNAT-UCstem1through DKK1-dependent modulation of WNT signalling
Authors: Coppola Arianna , Amoroso Filomena , Saracino Federica , Andolfi Gennaro , Sozzi Edoardo , Salerno Paolo , Zoppoli Pietro , Fiorenzano Alessandro , Merla Giuseppe , Patriarca Eduardo Jorge , Minchiotti Gabriella , Fico Annalisa 
Published: September 2024

ABSTRACTThe role and the mechanisms of long non-coding RNA (lncRNAs) in early mammalian embryogenesis remain unclear; this is mostly due to the complexity of the regulatory mechanism of lncRNAs and the limited availability of early embryo samples. The emergence of stem cell-based models of early mammalian embryogenesis offers new opportunities to address these challenging questions. Here we use mouse gastruloids to investigate the role of an ultraconserved lncRNA,T-UCstem1,in the formation of the mammalian body plan. Combining morphological and immunofluorescence analysis with bulk and single cells transcriptomics, we provide unprecedented evidence thatT-UCstem1is a key regulator of gastruloid development and is required for the extension of the anteroposterior axis. Specifically, knock down ofT-UCstem1results in aberrant gastruloid development, which is characterized by altered spatiotemporal expression of the differentiation markers and persistence of pluripotency genes. Single-cell analysis reveals higher cellular heterogeneity inT-UCstem1KD gastruloids. Notably, the presence of cell populations characterized by the co-expression of pluripotency and differentiation markers points to a key role ofT-UCstem1in establishment and maintenance of proper cellular identity. Mechanistically, we show thatT-UCstem1acts non-cell autonomously through Dickkopf-related protein 1 (DKK-1)-dependent modulation of WNT pathway. Our findings highlight a previously unexplored role for ultraconserved lncRNAs in gastruloid development and open the way for using gastruloids to dissect the functions of lncRNAs in early mammalian development.
Unsupervised alignment reveals structural commonalities and differences in neural representations of natural scenes across individuals and brain areas
Authors: Takeda Ken , Abe Kota , Kitazono Jun , Oizumi Masafumi 
Published: September 2024

AbstractNeuroscience research has extensively explored the commonality of neural representations of sensory stimuli across individuals to uncover universal neural mechanisms in the encoding of sensory information. To compare neural representations across different brains, Representational Similarity Analysis (RSA) has been used, which focuses on the similarity structures of neural representations for different stimuli. Despite the broad applicability and utility of RSA, one limitation is that its conventional framework assumes that neural representations of particular stimuli correspond directly to those of the same stimuli in different brains. This assumption excludes the possibility that neural representations correspond differently and limits the exploration of finer structural similarities. To overcome this limitation, we propose to use an unsupervised alignment framework based on Gromov-Wasserstein Optimal Transport (GWOT) to compare similarity structures without presupposing stimulus correspondences. This method allows for the identification of optimal correspondence between neural representations of stimuli based solely on internal neural representation relationships, and thereby provides a more detailed comparison of neural similarity structures across individuals. We applied this unsupervised alignment to investigate the commonality of representational similarity structures of natural scenes, using large datasets of Neuropixels recordings in mice and fMRI recordings in humans. We found that the similarity structure of neural representations in the same visual cortical areas can be well aligned across individuals in an unsupervised manner in both mice and humans. In contrast, we found that the degree of alignment across different brain areas cannot be fully explained by proximity in the visual processing hierarchy alone, but also found some reasonable alignment results, such that the similarity structures of higher-order visual areas can be well aligned with each other but not with lower-order visual areas. We expect that our unsupervised approach will be useful for revealing more detailed structural commonalities or differences that may not be captured by the conventional supervised approach.
Non-specific effect of double-stranded RNAs on Egyptian broomrape (Phelipanche aegyptiaca) seed germination
Authors: Zainali Nariman , Alizadeh Houshang , Alizadeh Hassan , Delavault Philippe 
Published: September 2024

AbstractObligate root parasitic plants of the Orobanchaceae family exhibit an intricate germination behavior. The host-dependent germination process of these parasites has prompted extensive research into effective control methods. While the effect of biomaterials such as amino acids and microRNA-encoded peptides have been explored, the effect of double-stranded RNAs (dsRNAs) has remained unexamined during the germination process. In this study, we asked whether an exogenously applied dsRNA can inhibit the germination of a root parasite, P. aegyptiaca. To this end, a dsRNA was designed to target theCYP707A1(dsCYP7), a marker gene of the chemically-dependent germination of broomrape seeds. Application of a concentrated dsCYP7 significantly reduced seed germination. However, two non-germination-specific dsRNAs designed to target mannose-6-phosphate reductase and green fluorescent protein brought about similar inhibitions. Moreover, applying rNTPs, which mimic RNA nitrogenous bases, also caused a similar reduction in the germination, suggesting that the non-specific inhibitory effect of the dsRNAs might arise from the nitrogenous moiety thereof. While, dsRNA application inhibited seed germination, their non-specific effects may pose a challenge for their application in studying root parasites germination, emphasizing on the need for further investigations.
Introducing circularity in early architectural design education
Authors: Campbell Emma , Niblock Chantelle , Flood Nuala , Lappin Sarah 
Published: September 2024

PurposeWith around 40% of global waste attributed to the built environment sector, architects play a significant role in how resources are consumed, produced and wasted. UK architectural educators have made good progress to embed climate emergency issues in design curricula but the challenges of resource use and waste, and the opportunities afforded by circular economy design principles are less well-considered. The purpose of this paper is to provide new insights on how to introduce circular design principles to early-stage architectural design students within university curricula.Design/methodology/approachThe study described took an experimental approach to designing design project briefs across several interlinked studio design projects for 1st-year Architecture students. Structured as a case study, each section describes the project, learning objectives, teaching methods and project reflections informed by a qualitative assessment of student development, outputs and feedback gathered through a questionnaire and focus group.FindingsIntroducing circular design early is highly beneficial to the development of knowledge on sustainability issues, critical design thinking and creative solution generation. Examples of beneficial teaching approaches include building systems thinking, facilitating collaboration, supporting learning-through-making, using simple analogies and referencing best-practice examples.Originality/valueThis research builds on limited existing circular design literature for built environment fields and through practical insights fills a significant knowledge gap on ways to introduce a complex and dynamic topic such as the circular economy to early-stage architectural design students as they develop fundamental discipline-specific knowledge, skills and competences.
Can big data analytics capability promote firm innovation? A moderated mediation model of organizational learning and market orientation
Authors: Song Moxi , Liao Yuanhong 
Published: September 2024

PurposeThe empirical results of the pivotal relationship between big data analytics capability (BDAC) and firm innovation remain inconclusive, necessitating a comprehensive understanding of the mediator and moderator through which firms can realize the potential innovation benefits of BDAC. Invoking the indirect perspective of dynamic capability theory, we constructed a moderated mediation model in which organizational learning mediates the impact of BDAC on firm innovation; the mediation effect of organizational learning is contingent upon market orientation.Design/methodology/approachOur hypotheses were tested using hierarchical regression and bootstrapping methods with a sample of 227 large- and medium-sized manufacturing firms in China.FindingsThe results reveal that both exploratory and exploitative learning fully mediate the link between BDAC and firm innovation. The mediation effect of exploitative learning is positively contingent upon market orientation; however, market orientation does not positively moderate the mediation effect of exploratory learning.Originality/valueOur moderated mediation model is one of the first to provide a fine-grained understanding of the process through which BDAC is transformed into firm innovation as well as the conditions under which this mediating mechanism may work effectively, thereby further elucidating the theoretical black box regarding the BDAC-firm innovation link and resolving existing debates in the literature regarding why BDAC does not always yield positive outcomes.