bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of Subsurface Control on the Coevolution of Hillslope Morphology and Runoff Generation
Authors: Litwin David G. , Harman Ciaran J. 
Published: October 2024

AbstractTopography is a key control on runoff generation, as topographic slope affects hydraulic gradients and curvature affects water flow paths. Simultaneously, runoff generation shapes topography through erosion, affecting landscape morphology over long timescales. Previous modeling efforts suggest that subsurface hydrological properties, relative to climate, are key mediators of this relationship. Specifically, when subsurface transmissivity and water storage capacity are low, (a) saturated areas and storm runoff should be larger and more variable, and (b) hillslopes shorter and lower relief, assuming other geomorphic factors are held constant. However, it remains uncertain whether subsurface properties can exert such strong controls on emergent properties in real landscapes. We compared emergent hydrological function and topography in two watersheds with very similar climatic and tectonic history, but very different subsurface properties due to contrasting bedrock lithology. We found that hillslopes were systematically shorter and saturated areas more dynamic at the lower transmissivity site. To test whether these features could be the result of coevolution between topography, hydrological function, and subsurface properties, we estimated all parameters of a coupled groundwater‐landscape evolution model for each site. Limitations were revealed in the model's ability to reproduce aspects of morphology and hydrologic behavior, however, model results suggested differences in hillslope length and variably saturated area between the sites could be explained by differences in subsurface properties, and not by differences in geomorphic process rates alone. This work demonstrates one way subsurface hydrology can profoundly affect landscape evolution.
Mechanisms of ferroptosis and targeted therapeutic approaches in urological malignancies
Authors: Ma Wenjie , Jiang Xiaotian , Jia Ruipeng , Li Yang 
Published: October 2024

AbstractThe prevalence of urological malignancies remains a significant global health concern, particularly given the challenging prognosis for patients in advanced disease stages. Consequently, there is a pressing need to explore the molecular mechanisms that regulate the development of urological malignancies to discover novel breakthroughs in diagnosis and treatment. Ferroptosis, characterized by iron-ion-dependent lipid peroxidation, is a form of programmed cell death (PCD) distinct from apoptosis, autophagy, and necrosis. Notably, lipid, iron, and glutathione metabolism intricately regulate intracellular ferroptosis, playing essential roles in the progression of various neoplasms and drug resistance. In recent years, ferroptosis has been found to be closely related to urological malignancies. This paper provides an overview of the involvement of ferroptosis in the pathogenesis and progression of urological malignancies, elucidates the molecular mechanisms governing its regulation, and synthesizes recent breakthroughs in diagnosing and treating these malignancies. We aim to provide a new direction for the clinical treatment of urological malignancies.
Elucidation of Spartina dimethylsulfoniopropionate synthesis genes enables engineering of stress tolerant plants
Authors: Payet Rocky D. , Bilham Lorelei J. , Kabir Shah Md Tamim , Monaco Serena , Norcott Ash R. , Allen Mellieha G. E. , Zhu Xiao-Yu , Davy Anthony J. , Brearley Charles A. , Todd Jonathan D. , Miller J. Benjamin 
Published: October 2024

AbstractThe organosulfur compound dimethylsulfoniopropionate (DMSP) has key roles in stress protection, global carbon and sulfur cycling, chemotaxis, and is a major source of climate-active gases. Saltmarshes are global hotspots for DMSP cycling due to Spartina cordgrasses that produce exceptionally high concentrations of DMSP. Here, in Spartina anglica, we identify the plant genes that underpin high-level DMSP synthesis: methionine S-methyltransferase (MMT), S-methylmethionine decarboxylase (SDC) and DMSP-amine oxidase (DOX). Homologs of these enzymes are common in plants, but differences in expression and catalytic efficiency explain why S. anglica accumulates such high DMSP concentrations and other plants only accumulate low concentrations. Furthermore, DMSP accumulation in S. anglica is consistent with DMSP having a role in oxidative and osmotic stress protection. Importantly, administration of DMSP by root uptake or over-expression of Spartina DMSP synthesis genes confers plant tolerance to salinity and drought offering a route for future bioengineering for sustainable crop production.
Genomic surveillance reveals a dengue 2 virus epidemic lineage with a marked decrease in sensitivity to Mosnodenvir
Authors: Bouzidi Hawa Sophia , Sen Selin , Piorkowski Géraldine , Pezzi Laura , Ayhan Nazli , Fontaine Albin , Canivez Thomas , Geulen Manon , Amaral Rayane , Grard Gilda , Durand Guillaume André , de Lamballerie Xavier , Touret Franck , Klitting Raphaëlle 
Published: October 2024

AbstractDengue fever is the most important arbovirosis for public health, with more than 5 million cases worldwide in 2023. Mosnodenvir is the first anti-dengue compound with very high preclinical pan-serotype activity, currently undergoing phase 2 clinical evaluation. Here, by analyzing dengue virus (DENV) genomes from the 2023-2024 epidemic in the French Caribbean Islands, we show that they all exhibit mutation NS4B:V91A, previously associated with a marked decrease in sensitivity to mosnodenvir in vitro. Using antiviral activity tests on four clinical and reverse-genetic strains, we confirm a marked decrease in mosnodenvir sensitivity for DENV-2 ( > 1000 fold). Finally, combining phylogenetic analysis and experimental testing for resistance, we find that virus lineages with low sensitivity to mosnodenvir due to the V91A mutation likely emerged multiple times over the last 30 years in DENV-2 and DENV-3. These results call for increased genomic surveillance, in particular to track lineages with resistance mutations. These efforts should allow to better assess the activity profile of DENV treatments in development against circulating strains.
Spatially resolved photoluminescence analysis of the role of Se in CdSexTe1−x thin films
Authors: Bowman A. R. , Leaver J. F. , Frohna K. , Stranks S. D. , Tagliabue G. , Major J. D. 
Published: October 2024

AbstractEvidence from cross-sectional electron microscopy has previously shown that Se passivates defects in CdSexTe1−x solar cells, and that this is the reason for better lifetimes and voltages in these devices. Here, we utilise spatially resolved photoluminescence measurements of CdSexTe1−x thin films on glass to directly study the effects of Se on carrier recombination in the material, isolated from the impact of conductive interfaces and without the need to prepare cross-sections through the samples. We find further evidence to support Se passivation of grain boundaries, but also identify an increase in below-bandgap photoluminescence that indicates the presence of Se-enhanced defects in grain interiors. Our results show that whilst Se treatment, in tandem with Cl passivation, does increase radiative efficiencies in CdSexTe1−x, it simultaneously increases the defect content within the grain interiors. This suggests that although it is beneficial overall, Se incorporation will still limit the maximum attainable optoelectronic properties of CdSexTe1−x thin films.
Mycobacterial HelD connects RNA polymerase recycling with transcription initiation
Authors: Kovaľ Tomáš , Borah Nabajyoti , Sudzinová Petra , Brezovská Barbora , Šanderová Hana , Vaňková Hausnerová Viola , Křenková Alena , Hubálek Martin , Trundová Mária , Adámková Kristýna , Dušková Jarmila , Schwarz Marek , Wiedermannová Jana , Dohnálek Jan , Krásný Libor , Kouba Tomáš 
Published: October 2024

AbstractMycobacterial HelD is a transcription factor that recycles stalled RNAP by dissociating it from nucleic acids and, if present, from the antibiotic rifampicin. The rescued RNAP, however, must disengage from HelD to participate in subsequent rounds of transcription. The mechanism of release is unknown. We show that HelD from Mycobacterium smegmatis forms a complex with RNAP associated with the primary sigma factor σA and transcription factor RbpA but not CarD. We solve several structures of RNAP-σA-RbpA-HelD without and with promoter DNA. These snapshots capture HelD during transcription initiation, describing mechanistic aspects of HelD release from RNAP and its protective effect against rifampicin. Biochemical evidence supports these findings, defines the role of ATP binding and hydrolysis by HelD in the process, and confirms the rifampicin-protective effect of HelD. Collectively, these results show that when HelD is present during transcription initiation, the process is protected from rifampicin until the last possible moment.
Unmasking AlphaFold to integrate experiments and predictions in multimeric complexes
Authors: Mirabello Claudio , Wallner Björn , Nystedt Björn , Azinas Stavros , Carroni Marta 
Published: October 2024

AbstractSince the release of AlphaFold, researchers have actively refined its predictions and attempted to integrate it into existing pipelines for determining protein structures. These efforts have introduced a number of functionalities and optimisations at the latest Critical Assessment of protein Structure Prediction edition (CASP15), resulting in a marked improvement in the prediction of multimeric protein structures. However, AlphaFold’s capability of predicting large protein complexes is still limited and integrating experimental data in the prediction pipeline is not straightforward. In this study, we introduce AF_unmasked to overcome these limitations. Our results demonstrate that AF_unmasked can integrate experimental information to build larger or hard to predict protein assemblies with high confidence. The resulting predictions can help interpret and augment experimental data. This approach generates high quality (DockQ score > 0.8) structures even when little to no evolutionary information is available and imperfect experimental structures are used as a starting point. AF_unmasked is developed and optimised to fill incomplete experimental structures (structural inpainting), which may provide insights into protein dynamics. In summary, AF_unmasked provides an easy-to-use method that efficiently integrates experiments to predict large protein complexes more confidently.
Demonstration of dual Shapiro steps in small Josephson junctions
Authors: Kaap Fabian , Kissling Christoph , Gaydamachenko Victor , Grünhaupt Lukas , Lotkhov Sergey 
Published: October 2024

AbstractBloch oscillations in small Josephson junctions were predicted theoretically as the quantum dual to Josephson oscillations. A significant consequence of this prediction is the emergence of quantized current steps, so-called dual Shapiro steps, when synchronizing Bloch oscillations to an external microwave signal. These steps potentially enable a fundamental standard of current I, defined via the frequency f of the external signal and the elementary charge e, I = ± n × 2ef, where n is a natural number. Here, we realize this fundamental relation by synchronizing the Bloch oscillations in small Al/AlOx/Al Josephson junctions to sinusoidal drives with frequencies from 1 to 6 GHz and observe dual Shapiro steps up to I ≈ 3 nA. Inspired by today’s voltage standards and to further confirm the duality relation, we investigate a pulsed drive regime and observe an asymmetric pattern of dual Shapiro steps. This work confirms quantum duality effects in Josephson junctions and paves the way towards a range of applications in quantum metrology based on well-established fabrication techniques and straightforward circuit design.
De novo production of protoberberine and benzophenanthridine alkaloids through metabolic engineering of yeast
Authors: Jiao Xiang , Fu Xiaozhi , Li Qishuang , Bu Junling , Liu Xiuyu , Savolainen Otto , Huang Luqi , Guo Juan , Nielsen Jens , Chen Yun 
Published: October 2024

AbstractProtoberberine alkaloids and benzophenanthridine alkaloids (BZDAs) are subgroups of benzylisoquinoline alkaloids (BIAs), which represent a diverse class of plant-specialized natural metabolites with many pharmacological properties. Microbial biosynthesis has been allowed for accessibility and scalable production of high-value BIAs. Here, we engineer Saccharomyces cerevisiae to de novo produce a series of protoberberines and BZDAs, including palmatine, berberine, chelerythrine, sanguinarine and chelirubine. An ER compartmentalization strategy is developed to improve vacuole protein berberine bridge enzyme (BBE) activity, resulting in >200% increase on the production of the key intermediate (S)-scoulerine. Another promiscuous vacuole protein dihydrobenzophenanthridine oxidase (DBOX) has been identified to catalyze two-electron oxidation on various tetrahydroprotoberberines at N7-C8 position and dihydrobenzophenanthridine alkaloids. Furthermore, cytosolically expressed DBOX can alleviate the limitation on BBE. This study highlights the potential of microbial cell factories for the biosynthesis of a diverse group of BIAs through engineering of heterologous plant enzymes.
Structural basis for antibiotic transport and inhibition in PepT2
Authors: Parker Joanne L. , Deme Justin C. , Lichtinger Simon M. , Kuteyi Gabriel , Biggin Philip C. , Lea Susan M. , Newstead Simon 
Published: October 2024

AbstractThe uptake and elimination of beta-lactam antibiotics in the human body are facilitated by the proton-coupled peptide transporters PepT1 (SLC15A1) and PepT2 (SLC15A2). The mechanism by which SLC15 family transporters recognize and discriminate between different drug classes and dietary peptides remains unclear, hampering efforts to improve antibiotic pharmacokinetics through targeted drug design and delivery. Here, we present cryo-EM structures of the proton-coupled peptide transporter, PepT2 from Rattus norvegicus, in complex with the widely used beta-lactam antibiotics cefadroxil, amoxicillin and cloxacillin. Our structures, combined with pharmacophore mapping, molecular dynamics simulations and biochemical assays, establish the mechanism of beta-lactam antibiotic recognition and the important role of protonation in drug binding and transport.
Cycling of labile and recalcitrant carboxyl-rich alicyclic molecules and carbohydrates in Baffin Bay
Authors: McKee Kayla , Abdulla Hussain , O’Reilly Lauren , Walker Brett D. 
Published: October 2024

AbstractMarine dissolved organic matter (DOM) is an important, actively cycling carbon reservoir (662 GtC). However, the chemical structure and cycling of DOM within rapidly warming, polar environments remains largely unconstrained. Previous studies have shown rapid surface cycling of carbohydrates as biologically-labile DOM (LDOM). Conversely, carboxyl-rich alicyclic molecules (CRAM) are often used as examples of biologically-recalcitrant DOM (RDOM). Traditional DOM isolation methods (e.g., ultrafiltration (10–30% of DOM) and solid-phase extraction (40–60% of DOM) induce chemical-, size- and compositional-bias – complicating inferences to total DOM cycling. Here, we use a total DOM proton (1H) nuclear magnetic resonance (NMR) spectroscopy method to show carbohydrates and CRAM have high concentrations in the surface ocean and low concentrations at depth in Baffin Bay. Between 21–43% of surface CRAM is removed at depth. These results suggest both CRAM and carbohydrates are major LDOM constituents – contradicting the existing CRAM cycling paradigm and further constraining the long-term persistence of deep ocean DOM.
Referral to pulmonary rehabilitation and palliative care services in people with idiopathic pulmonary fibrosis in England, 2010–2019
Authors: Morgan Ann D. , Khan Hakeem , George Peter M. , Quint Jennifer K. 
Published: October 2024

AbstractThe benefits of pulmonary rehabilitation (PR) and palliative care (PC) as non-pharmacological therapies for people with idiopathic pulmonary fibrosis (IPF) are increasingly being recognised but in the UK the proportion of people with this life-limiting condition who are referred to such services is thought to be low. This retrospective cohort study aimed to describe trends in referrals to PR and PC services among people with IPF over a 10-year period and to identify factors associated with non-referral. Our study cohort was drawn from the UK’s pseudonymised Clinical Practice Research Datalink (CPRD) Aurum primary care database and comprised 17,071 individuals diagnosed with IPF between 2010 and 2019. While 12.0% of IPF patients were offered a referral to PR, less than 2% completed a PR programme. Around a fifth (19.4%) received a referral to generic PC support services; however, this is well below reported PC referral rates for lung cancer patients. Moreover, the majority of PC referrals occurred late; among those who died, 31% were referred within a month and 70% within 6 months of death. Referrals to PR and PC had however increased (by around 2–fold and 4-fold, respectively) over the course of the study period. Factors associated with non-referral to PR included female sex, older age and co-diagnosis of dementia; barriers to PC referral included being female or of Asian or Black ethnicity. We also found evidence of regional differences in referrals. These findings confirm that PR and PC service provision for people with IPF across England is suboptimal.
Systems immunology approaches to study T cells in health and disease
Authors: Yang Aaron , Poholek Amanda C. 
Published: October 2024

AbstractT cells are dynamically regulated immune cells that are implicated in a variety of diseases ranging from infection, cancer and autoimmunity. Recent advancements in sequencing methods have provided valuable insights in the transcriptional and epigenetic regulation of T cells in various disease settings. In this review, we identify the key sequencing-based methods that have been applied to understand the transcriptomic and epigenomic regulation of T cells in diseases.
PRN: progressive reasoning network and its image completion applications
Authors: Zhang Yongqin , Wang Xiaoyu , Zhu Panpan , Lu Xuan , Xiao Jinsheng , Zhou Wei , Li Zhan , Peng Xianlin 
Published: October 2024

AbstractAncient murals embody profound historical, cultural, scientific, and artistic values, yet many are afflicted with challenges such as pigment shedding or missing parts. While deep learning-based completion techniques have yielded remarkable results in restoring natural images, their application to damaged murals has been unsatisfactory due to data shifts and limited modeling efficacy. This paper proposes a novel progressive reasoning network designed specifically for mural image completion, inspired by the mural painting process. The proposed network comprises three key modules: a luminance reasoning module, a sketch reasoning module, and a color fusion module. The first two modules are based on the double-codec framework, designed to infer missing areas’ luminance and sketch information. The final module then utilizes a paired-associate learning approach to reconstruct the color image. This network utilizes two parallel, complementary pathways to estimate the luminance and sketch maps of a damaged mural. Subsequently, these two maps are combined to synthesize a complete color image. Experimental results indicate that the proposed network excels in restoring clearer structures and more vivid colors, surpassing current state-of-the-art methods in both quantitative and qualitative assessments for repairing damaged images. Our code and results will be publicly accessible athttps://github.com/albestobe/PRN.
The functional roles of zebrafish HoxA- and HoxD-related clusters in the pectoral fin development
Authors: Ishizaka Mizuki , Maeno Akiteru , Nakazawa Hidemichi , Fujii Renka , Oikawa Sae , Tani Taisei , Kanno Haruna , Koita Rina , Kawamura Akinori 
Published: October 2024

AbstractThe paralogs 9–13 Hox genes in mouse HoxA and HoxD clusters are critical for limb development. When both HoxA and HoxD clusters are deleted in mice, significant limb truncation is observed compared to the phenotypes of single and compound mutants of Hox9-13 genes in these clusters. In zebrafish, mutations in hox13 genes in HoxA- and HoxD-related clusters result in abnormal morphology of pectoral fins, homologous to forelimbs. However, the effect of the simultaneous deletions of entire HoxA- and HoxD-related clusters on pectoral fin development remains unknown. Here, we generated mutants with several combinations of hoxaa, hoxab, and hoxda cluster deletions and analyzed the pectoral fin development. In hoxaa−/−;hoxab−/−;hoxda−/− larvae, the endoskeletal disc and the fin-fold are significantly shortened in developing pectoral fins. In addition, we show that this anomaly is due to defects in the pectoral fin growth after the fin bud formation. Furthermore, in the surviving adult mutants, micro-CT scanning reveals defects in the posterior portion of the pectoral fin which is thought to represent latent regions of the limb. Our results further support that the functional role of HoxA and HoxD clusters is conserved in the paired appendage formation in bony fishes.
Application of physiological network mapping in the prediction of survival in critically ill patients with acute liver failure
Authors: Oyelade Tope , Moore Kevin P. , Mani Ali R. 
Published: October 2024

AbstractReduced functional connectivity of physiological systems is associated with poor prognosis in critically ill patients. However, physiological network analysis is not commonly used in clinical practice and awaits quantitative evidence. Acute liver failure (ALF) is associated with multiorgan failure and mortality. Prognostication in ALF is highly important for clinical management but is currently dependent on models that do not consider the interaction between organ systems. This study aims to examine whether physiological network analysis can predict survival in patients with ALF. Data from 640 adult patients admitted to the ICU for paracetamol-induced ALF were extracted from the MIMIC-III database. Parenclitic network analysis was performed on the routine biomarkers using 28-day survivors as reference population and network clusters were identified for survivors and non-survivors using k-clique percolation method. Network analysis showed that liver function biomarkers were more clustered in survivors than in non-survivors. Arterial pH was also found to cluster with serum creatinine and bicarbonate in survivors compared with non-survivors, where it clustered with respiratory nodes indicating physiologically distinctive compensatory mechanism. Deviation along the pH-bicarbonate and pH-creatinine axes significantly predicts mortality independent of current prognostic indicators. These results demonstrate that network analysis can provide pathophysiologic insight and predict survival in critically ill patients with ALF.