bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI
Authors: Molina Jonathan J. , Kohler Kurt N. , Gager Christopher , Andersen Marissa J. , Wongso Ellsa , Lucas Elizabeth R. , Paik Andrew , Xu Wei , Donahue Deborah L. , Bergeron Karla , Klim Aleksandra , Caparon Michael G. , Hultgren Scott J. , Desai Alana , Ploplis Victoria A. , Flick Matthew J. , Castellino Francis J. , Flores-Mireles Ana L. 
Published: March 2024

AbstractCatheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat partly due to development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, here we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition in the catheterized bladder, are predisposed to severe CAUTI and septicemia by diverse uropathogens in mono- and poly-microbial infections. Furthermore, here we found that Enterococcus faecalis, a prevalent CAUTI pathogen, uses the secreted protease, SprE, to induce fibrin accumulation and create a niche ideal for growth, biofilm formation, and persistence during CAUTI.
Diverse roles of the metal binding domains and transport mechanism of copper transporting P-type ATPases
Authors: Guo Zongxin , Orädd Fredrik , Bågenholm Viktoria , Grønberg Christina , Ma Jian Feng , Ott Peter , Wang Yong , Andersson Magnus , Pedersen Per Amstrup , Wang Kaituo , Gourdon Pontus 
Published: March 2024

AbstractCopper transporting P-type (P1B-1-) ATPases are essential for cellular homeostasis. Nonetheless, the E1-E1P-E2P-E2 states mechanism of P1B-1-ATPases remains poorly understood. In particular, the role of the intrinsic metal binding domains (MBDs) is enigmatic. Here, four cryo-EM structures and molecular dynamics simulations of a P1B-1-ATPase are combined to reveal that in many eukaryotes the MBD immediately prior to the ATPase core, MBD−1, serves a structural role, remodeling the ion-uptake region. In contrast, the MBD prior to MBD−1, MBD−2, likely assists in copper delivery to the ATPase core. Invariant Tyr, Asn and Ser residues in the transmembrane domain assist in positioning sulfur-providing copper-binding amino acids, allowing for copper uptake, binding and release. As such, our findings unify previously conflicting data on the transport and regulation of P1B-1-ATPases. The results are critical for a fundamental understanding of cellular copper homeostasis and for comprehension of the molecular bases of P1B-1-disorders and ongoing clinical trials.
Insights into the modulation of bacterial NADase activity by phage proteins
Authors: Yin Hang , Li Xuzichao , Wang Xiaoshen , Zhang Chendi , Gao Jiaqi , Yu Guimei , He Qiuqiu , Yang Jie , Liu Xiang , Wei Yong , Li Zhuang , Zhang Heng 
Published: March 2024

AbstractThe Silent Information Regulator 2 (SIR2) protein is widely implicated in antiviral response by depleting the cellular metabolite NAD+. The defense-associated sirtuin 2 (DSR2) effector, a SIR2 domain-containing protein, protects bacteria from phage infection by depleting NAD+, while an anti-DSR2 protein (DSR anti-defense 1, DSAD1) is employed by some phages to evade this host defense. The NADase activity of DSR2 is unleashed by recognizing the phage tail tube protein (TTP). However, the activation and inhibition mechanisms of DSR2 are unclear. Here, we determine the cryo-EM structures of DSR2 in multiple states. DSR2 is arranged as a dimer of dimers, which is facilitated by the tetramerization of SIR2 domains. Moreover, the DSR2 assembly is essential for activating the NADase function. The activator TTP binding would trigger the opening of the catalytic pocket and the decoupling of the N-terminal SIR2 domain from the C-terminal domain (CTD) of DSR2. Importantly, we further show that the activation mechanism is conserved among other SIR2-dependent anti-phage systems. Interestingly, the inhibitor DSAD1 mimics TTP to trap DSR2, thus occupying the TTP-binding pocket and inhibiting the NADase function. Together, our results provide molecular insights into the regulatory mechanism of SIR2-dependent NAD+ depletion in antiviral immunity.
Substrate metabolism in male astronauts onboard the International Space Station: the ENERGY study
Authors: Le Roux Elisa , Zahariev Alexandre , Chery Isabelle , Schoeller Dale A. , Bourdier Pierre , Maillet Alain , Thevenot Cecile , Garnotel Maël , Gauquelin-Koch Guillemette , Van Den Berghe Laurie , Blanc Stéphane , Simon Chantal , Bergouignan Audrey 
Published: March 2024

AbstractBedrest shifts fasting and postprandial fuel selection towards carbohydrate use over lipids, potentially affecting astronauts’ performance and health. We investigated whether this change occurs in astronauts after at least 3 months onboard the International Space Station (ISS). We further explored the associations with diet, physical activity (PA), and body composition. Before and during spaceflight, respiratory quotient (RQ), carbohydrate, and fat oxidation were measured by indirect calorimetry before and following a standardized meal in 11 males (age = 45.7 [SD 7.7] years, BMI = 24.3 [2.1] kg m−²). Postprandial substrate use was determined by 0-to-260 min postprandial incremental area under the curve (iAUC) of nutrient oxidation and the difference between maximal postprandial and fasting RQ (ΔRQ). Food quotient (FQ) was calculated from diet logs. Fat (FM) and fat-free mass (FFM) were measured by hydrometry and PA by accelerometry and diary logs. Spaceflight increased fasting RQ (P = 0.01) and carbohydrate oxidation (P = 0.04) and decreased fasting lipid oxidation (P < 0.01). An increase in FQ (P < 0.001) indicated dietary modifications onboard the ISS. Spaceflight-induced RQ changes adjusted for ground RQ correlated with inflight FQ (P < 0.01). In postprandial conditions, nutrient oxidation and ΔRQ were unaffected on average. Lipid oxidation changes negatively correlated with FFM changes and inflight aerobic exercise and positively with FM changes. The opposite was observed for carbohydrate oxidation. ΔRQ changes were negatively and positively related to FM and FFM changes, respectively. In conclusion, fasting substrate oxidation shift observed during spaceflight may primarily result from dietary modifications. Between-astronaut variability in postprandial substrate oxidation depends on body composition changes and inflight PA.
Structural insights into the mechanism of protein transport by the Type 9 Secretion System translocon
Authors: Lauber Frédéric , Deme Justin C. , Liu Xiaolong , Kjær Andreas , Miller Helen L. , Alcock Felicity , Lea Susan M. , Berks Ben C. 
Published: March 2024

AbstractSecretion systems are protein export machines that enable bacteria to exploit their environment through the release of protein effectors. The Type 9 Secretion System (T9SS) is responsible for protein export across the outer membrane (OM) of bacteria of the phylum Bacteroidota. Here we trap the T9SS of Flavobacterium johnsoniae in the process of substrate transport by disrupting the T9SS motor complex. Cryo-EM analysis of purified substrate-bound T9SS translocons reveals an extended translocon structure in which the previously described translocon core is augmented by a periplasmic structure incorporating the proteins SprE, PorD and a homologue of the canonical periplasmic chaperone Skp. Substrate proteins bind to the extracellular loops of a carrier protein within the translocon pore. As transport intermediates accumulate on the translocon when energetic input is removed, we deduce that release of the substrate–carrier protein complex from the translocon is the energy-requiring step in T9SS transport.
A figure of merit for efficiency roll-off in TADF-based organic LEDs
Authors: Diesing S. , Zhang L. , Zysman-Colman E. , Samuel I. D. W. 
Published: March 2024

AbstractOrganic light-emitting diodes (OLEDs) are a revolutionary light-emitting display technology that has been successfully commercialized in mobile phones and televisions1,2. The injected charges form both singlet and triplet excitons, and for high efficiency it is important to enable triplets as well as singlets to emit light. At present, materials that harvest triplets by thermally activated delayed fluorescence (TADF) are a very active field of research as an alternative to phosphorescent emitters that usually use heavy metal atoms3,4. Although excellent progress has been made, in most TADF OLEDs there is a severe decrease of efficiency as the drive current is increased, known as efficiency roll-off. So far, much of the literature suggests that efficiency roll-off should be reduced by minimizing the energy difference between singlet and triplet excited states (ΔEST) to maximize the rate of conversion of triplets to singlets by means of reverse intersystem crossing (kRISC)5–20. We analyse the efficiency roll-off in a wide range of TADF OLEDs and find that neither of these parameters fully accounts for the reported efficiency roll-off. By considering the dynamic equilibrium between singlets and triplets in TADF materials, we propose a figure of merit for materials design to reduce efficiency roll-off and discuss its correlation with reported data of TADF OLEDs. Our new figure of merit will guide the design and development of TADF materials that can reduce efficiency roll-off. It will help improve the efficiency of TADF OLEDs at realistic display operating conditions and expand the use of TADF materials to applications that require high brightness, such as lighting, augmented reality and lasing.
High-fidelity spin qubit operation and algorithmic initialization above 1 K
Authors: Huang Jonathan Y. , Su Rocky Y. , Lim Wee Han , Feng MengKe , van Straaten Barnaby , Severin Brandon , Gilbert Will , Dumoulin Stuyck Nard , Tanttu Tuomo , Serrano Santiago , Cifuentes Jesus D. , Hansen Ingvild , Seedhouse Amanda E. , Vahapoglu Ensar , Leon Ross C. C. , Abrosimov Nikolay V. , Pohl Hans-Joachim , Thewalt Michael L. W. , Hudson Fay E. , Escott Christopher C. , Ares Natalia , Bartlett Stephen D. , Morello Andrea , Saraiva Andre , Laucht Arne , Dzurak Andrew S. , Yang Chih Hwan 
Published: March 2024

AbstractThe encoding of qubits in semiconductor spin carriers has been recognized as a promising approach to a commercial quantum computer that can be lithographically produced and integrated at scale1–10. However, the operation of the large number of qubits required for advantageous quantum applications11–13 will produce a thermal load exceeding the available cooling power of cryostats at millikelvin temperatures. As the scale-up accelerates, it becomes imperative to establish fault-tolerant operation above 1 K, at which the cooling power is orders of magnitude higher14–18. Here we tune up and operate spin qubits in silicon above 1 K, with fidelities in the range required for fault-tolerant operations at these temperatures19–21. We design an algorithmic initialization protocol to prepare a pure two-qubit state even when the thermal energy is substantially above the qubit energies and incorporate radiofrequency readout to achieve fidelities up to 99.34% for both readout and initialization. We also demonstrate single-qubit Clifford gate fidelities up to 99.85% and a two-qubit gate fidelity of 98.92%. These advances overcome the fundamental limitation that the thermal energy must be well below the qubit energies for the high-fidelity operation to be possible, surmounting a main obstacle in the pathway to scalable and fault-tolerant quantum computation.
The complex polyploid genome architecture of sugarcane
Authors: Healey A. L. , Garsmeur O. , Lovell J. T. , Shengquiang S. , Sreedasyam A. , Jenkins J. , Plott C. B. , Piperidis N. , Pompidor N. , Llaca V. , Metcalfe C. J. , Doležel J. , Cápal P. , Carlson J. W. , Hoarau J. Y. , Hervouet C. , Zini C. , Dievart A. , Lipzen A. , Williams M. , Boston L. B. , Webber J. , Keymanesh K. , Tejomurthula S. , Rajasekar S. , Suchecki R. , Furtado A. , May G. , Parakkal P. , Simmons B. A. , Barry K. , Henry R. J. , Grimwood J. , Aitken K. S. , Schmutz J. , D’Hont A. 
Published: March 2024

AbstractSugarcane, the world’s most harvested crop by tonnage, has shaped global history, trade and geopolitics, and is currently responsible for 80% of sugar production worldwide1. While traditional sugarcane breeding methods have effectively generated cultivars adapted to new environments and pathogens, sugar yield improvements have recently plateaued2. The cessation of yield gains may be due to limited genetic diversity within breeding populations, long breeding cycles and the complexity of its genome, the latter preventing breeders from taking advantage of the recent explosion of whole-genome sequencing that has benefited many other crops. Thus, modern sugarcane hybrids are the last remaining major crop without a reference-quality genome. Here we take a major step towards advancing sugarcane biotechnology by generating a polyploid reference genome for R570, a typical modern cultivar derived from interspecific hybridization between the domesticated species (Saccharum officinarum) and the wild species (Saccharum spontaneum). In contrast to the existing single haplotype (‘monoploid’) representation of R570, our 8.7 billion base assembly contains a complete representation of unique DNA sequences across the approximately 12 chromosome copies in this polyploid genome. Using this highly contiguous genome assembly, we filled a previously unsized gap within an R570 physical genetic map to describe the likely causal genes underlying the single-copy Bru1 brown rust resistance locus. This polyploid genome assembly with fine-grain descriptions of genome architecture and molecular targets for biotechnology will help accelerate molecular and transgenic breeding and adaptation of sugarcane to future environmental conditions.
Multi-organ single-cell transcriptomics of immune cells uncovered organ-specific gene expression and functions
Authors: Tsagiopoulou Maria , Rashmi Sonal , Aguilar-Fernandez Sergio , Nieto Juan , Gut Ivo G. 
Published: March 2024

AbstractDespite the wealth of publicly available single-cell datasets, our understanding of distinct resident immune cells and their unique features in diverse human organs remains limited. To address this, we compiled a meta-analysis dataset of 114,275 CD45+ immune cells sourced from 14 organs in healthy donors. While the transcriptome of immune cells remains relatively consistent across organs, our analysis has unveiled organ-specific gene expression differences (GTPX3 in kidney, DNTT and ACVR2B in thymus). These alterations are linked to different transcriptional factor activities and pathways including metabolism. TNF-α signaling through the NFkB pathway was found in several organs and immune compartments. The presence of distinct expression profiles for NFkB family genes and their target genes, including cytokines, underscores their pivotal role in cell positioning. Taken together, immune cells serve a dual role: safeguarding the organs and dynamically adjusting to the intricacies of the host organ environment, thereby actively contributing to its functionality and overall homeostasis.
Compound Matrix-Based Project Database (CMPD)
Authors: Kosztyán Zsolt T. , Novák Gergely L. 
Published: March 2024

AbstractThe impact of projects is vital, from business operations to research to the national economy. Therefore, management science and operation research have extensively studied project scheduling and resource allocation for over six decades. Project databases were proposed to test algorithms, including simulated or real, single or multiprojects, and single-mode or multi-mode projects. However, the dozens of project databases are extremely heterogeneous regarding the file structure and the features of the modeled projects. Furthermore, the efficiency and performance of project scheduling and resource allocation algorithms are susceptible to the characteristics of projects. Therefore, the proposed Compound Matrix-Based Project Database (CMPD) collects and consolidates the most frequently used project databases. The proposed Unified Matrix-Based Project-Planning Model (UMP) sparse matrix-based model enables the addition of new features to existing project structures, such as completion priorities, structural flexibility, and quality parameters, to broaden the scope of considered projects and to take account of flexible approaches, such as agile, extreme, and hybrid projects.
The evolutionary dynamics of how languages signal who does what to whom
Authors: Shcherbakova Olena , Blasi Damián E. , Gast Volker , Skirgård Hedvig , Gray Russell D. , Greenhill Simon J. 
Published: March 2024

AbstractLanguages vary in how they signal “who does what to whom”. Three main strategies to indicate the participant roles of “who” and “whom” are case, verbal indexing, and rigid word order. Languages that disambiguate these roles with case tend to have either verb-final or flexible word order. Most previous studies that found these patterns used limited language samples and overlooked the causal mechanisms that could jointly explain the association between all three features. Here we analyze grammatical data from a Grambank sample of 1705 languages with phylogenetic causal graph methods. Our results corroborate the claims that verb-final word order generally gives rise to case and, strikingly, establish that case tends to lead to the development of flexible word order. The combination of novel statistical methods and the Grambank database provides a model for the rigorous testing of causal claims about the factors that shape patterns of linguistic diversity.
Vitamin D3 deficiency and osteopenia in spastic paraplegia type 5 indicate impaired bone homeostasis
Authors: Ehnert Sabrina , Hauser Stefan , Hengel Holger , Höflinger Philip , Schüle Rebecca , Lindig Tobias , Baets Jonathan , Deconinck Tine , de Jonghe Peter , Histing Tina , Nüssler Andreas K. , Schöls Ludger , Rattay Tim W. 
Published: March 2024

AbstractHereditary spastic paraplegia type 5 (SPG5) is an autosomal recessively inherited movement disorder characterized by progressive spastic gait disturbance and afferent ataxia. SPG5 is caused by bi-allelic loss of function mutations in CYP7B1 resulting in accumulation of the oxysterols 25-hydroxycholesterol and 27-hydroxycholesterol in serum and cerebrospinal fluid of SPG5 patients. An effect of 27- hydroxycholesterol via the estrogen and liver X receptors was previously shown on bone homeostasis. This study analyzed bone homeostasis and osteopenia in 14 SPG5 patients as a non-motor feature leading to a potential increased risk for bone fractures. T-Scores in CT bone density measurements were reduced, indicating osteopenia in SPG5 patients. Further, we analyzed various metabolites of bone homeostasis by ELISA in serum samples of these patients. We identified a lack of vitamin D3 metabolites (Calcidiol and Calcitriol), an increase in Sclerostin as a bone formation/mineralization inhibiting factor, and a decrease in cross-linked N-telopeptide of type I collagen (NTX), a marker indicating reduced bone resorption. As statin treatment has been found to lower oxysterol levels, we evaluated its effect in samples of the STOP-SPG5 trial and found atorvastatin to normalize the increased sclerostin levels. In summary, our study identified osteopenia as a non-motor feature in SPG5 and suggests the need for vitamin D3 substitution in SPG5 patients. Sclerostin may be considered a therapeutic target and biomarker in upcoming therapeutical trials in SPG5.
Cretaceous to early Paleogene sediment provenance transition from continental to magmatic arc systems in the Northwestern Pacific Region
Authors: Harisma Harisma , Niki Sota , Hirata Takafumi , Naruse Hajime 
Published: March 2024

AbstractUnraveling the Paleo-Kuril Arc's origins is key to understanding northwest Pacific tectonics. The Paleo-Kuril Arc is viewed as an intraoceanic arc from trench subduction between the Izanagi and Pacific Plates. Alternatively, several studies suggest the Paleo-Kuril Arc as a continental magmatic arc, hypothesizing the existence of a mid-oceanic ridge and Paleogene subduction, placing the Paleo-Kuril Arc near the Okhotsk Block's southern edge. This study clarifies these hypotheses, previously clouded by limited geochronological data on deposits in the Paleo-Kuril Arc. We conducted U–Pb dating to examine the origins of detrital zircons from the Cretaceous–Paleogene Tokoro and Nemuro Belts of the Paleo-Kuril Arc. Cluster analysis, merging new and existing data, identified two unique detrital zircon age clusters. The abundance of Precambrian zircons in Cretaceous–Paleocene Paleo-Kuril Arc sandstones (Type 1 Cluster) suggests a continental magmatic origin, supporting the ridge subduction model. However, an early Eocene shift to a consistent local volcanic source (Type 2 Cluster) highlights a significant provenance change. This geochronological evidence, indicating a separation from continental sources, calls for further research to decode the simultaneous development of sediment sources in different geological belts, potentially tied to the ridge subduction event.
Hypoxia drives shared and distinct transcriptomic changes in two invasive glioma stem cell lines
Authors: Marallano Valerie J. , Ughetta Mary E. , Tejero Rut , Nanda Sidhanta , Ramalingam Rohana , Stalbow Lauren , Sattiraju Anirudh , Huang Yong , Ramakrishnan Aarthi , Shen Li , Wojcinski Alexandre , Kesari Santosh , Zou Hongyan , Tsankov Alexander M. , Friedel Roland H. 
Published: March 2024

AbstractGlioblastoma (GBM) is the most common primary malignant cancer of the central nervous system. Insufficient oxygenation (hypoxia) has been linked to GBM invasion and aggression, leading to poor patient outcomes. Hypoxia induces gene expression for cellular adaptations. However, GBM is characterized by high intertumoral (molecular subtypes) and intratumoral heterogeneity (cell states), and it is not well understood to what extent hypoxia triggers patient-specific gene responses and cellular diversity in GBM. Here, we surveyed eight patient-derived GBM stem cell lines for invasion phenotypes in 3D culture, which identified two GBM lines showing increased invasiveness in response to hypoxia. RNA-seq analysis of the two patient GBM lines revealed a set of shared hypoxia response genes concerning glucose metabolism, angiogenesis, and autophagy, but also a large set of patient-specific hypoxia-induced genes featuring cell migration and anti-inflammation, highlighting intertumoral diversity of hypoxia responses in GBM. We further applied the Shared GBM Hypoxia gene signature to single cell RNA-seq datasets of glioma patients, which showed that hypoxic cells displayed a shift towards mesenchymal-like (MES) and astrocyte-like (AC) states. Interestingly, in response to hypoxia, tumor cells in IDH-mutant gliomas displayed a strong shift to the AC state, whereas tumor cells in IDH-wildtype gliomas mainly shifted to the MES state. This distinct hypoxia response of IDH-mutant gliomas may contribute to its more favorable prognosis. Our transcriptomic studies provide a basis for future approaches to better understand the diversity of hypoxic niches in gliomas.