bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review and meta-analysis of protocols and yield of direct from sputum sequencing ofMycobacterium tuberculosis
Authors: Mann B.C. , Loubser J. , Omar S. , Glanz C. , Ektefaie Y. , Jacobson K.R. , Warren R.M. , Farhat M.R. 
Published: December 2024

AbstractDirect sputum whole genome sequencing (dsWGS) can revolutionizeMycobacterium tuberculosis(Mtb) diagnosis by enabling rapid detection of drug resistance and strain diversity without the biohazard of culture. We searched PubMed, Web of Science and Google scholar, and identified 8 studies that met inclusion criteria for testing protocols for dsWGS. Utilising meta-regression we identify several key factors positively associated with dsWGS success, including higherMtbbacillary load, mechanical disruption, and enzymatic/chemical lysis. Specifically, smear grades of 3+ (OR = 14.7, 95% CI: 3.5, 62.1; p = 0.0005) were strongly associated with improved outcomes, whereas decontamination with sodium hydroxide (NaOH) was negatively associated (OR = 0.005, 95% CI: 0.001, 0.03; p = 7e-06), likely due to its harsh effects onMtbcells. Furthermore, mechanical lysis (OR = 193.3, 95% CI: 11.7, 3197.8; p = 0.008) and enzymatic/chemical lysis (OR = 18.5, 95% CI: 1.9, 183.1; p = 0.02) were also strongly associated with improved dsWGS. Across the studies, we observed a high degree of variability in approaches to sputum pre-processing prior to dsWGS highlighting the need for standardized best practices. In particular we conclude that optimizing pre-processing steps including decontamination with the exploration of alternatives to NaOH to better preserve Mtb cells and DNA, and best practices for cell lysis during DNA extraction as priorities. Further and considering the strong association betweenMtbload and successful dsWGS, protocol improvements for optimal sputum sample collection, handling, and storage could also further enhance the success rate of dsWGS.
Non-shivering thermogenesis is intact upon brown-adipocyte specific loss of ATGL and HSL due to white adipose tissue browning
Authors: Manandhar Yelina , Pirchheim Anita , Hofer Peter , Vujic Nemanja , Kolb Dagmar , Hoefler Gerald , Kratky Dagmar , Schweiger Martina , Taschler Ulrike , Zimmermann Robert , Zechner Rudolf , Schreiber Renate 
Published: December 2024

SummaryIntracellular fatty acids (FAs) activate and fuel non-shivering thermogenesis (NST) mediated via uncoupling protein 1 (UCP1). Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are the two main triacylglycerol lipases in adipocytes that control FA availability. We showed previously that a brown adipocyte-specific loss of ATGL does not affect cold-induced thermogenesis in brown adipose tissue (BAT) and NST, raising the question whether HSL-mediated FA release is sufficient to allow NST. Here, we show that a brown adipocyte-specific loss of both ATGL and HSL in mice leads to impaired BAT thermogenic capacity in cold, but still allows normal NST. The BAT defect is attributed to an impaired abundance of mitochondria as well as reduced oxidative capacity despite increased adipocyte numbers in BAT. Notably, the reduced thermogenesis in BAT of BAT-iDAKO mice leads to a concomitant upregulation of UCP1 expression (browning) in white adipose tissue (WAT) indicating that thermogenesis partially shifts from BAT towards WAT. In accordance with this assumption, genetic loss of ATGL and HSL in both BAT and WAT leads to dysfunctional BAT thermogenesis and defective browning in WAT resulting in blunted NST. Our study highlights the metabolic adaptability of adipose tissue and the critical role of intracellular lipolysis in the regulation of thermogenesis.
Structure of the human taurine transporter TauT reveals substrate recognition and mechanisms of inhibition
Authors: Lu Yishuo , Ding Dian , Chen Hongyi , Jiang Peijun , Yin Yuxin 
Published: December 2024

AbstractTaurine, a sulfur-containing amino acid, plays a crucial role in human health due to its antioxidant, anti-inflammatory, osmoregulatory properties1,2. Taurine levels are primarily regulated by the sodium-/chloride-dependent taurine transporter (TauT)3. Inhibitors of TauT have potential in the treatment of certain diseases, including neurological disorders and cancer4,5. Here, we present five structures of TauT: in the substrate-free apo state, in complex with taurine and in complex with taurine-mimetic inhibitors β-alanine, GABA and guanidinoethyl sulfonate (GES), each with varying length of linear structure, in both inward-facing and occluded conformations. The taurine-, β-alanine- and GABA-bound hTauT structures, in the presence of NaCl, adopt an occluded conformation, with ligands binding in the central pocket. In the presence of KCl, GES-bound hTauT adopts an inward-facing conformation, with two molecules positioned along the substrate translocation pathway with one into the deep central cavity and the other precluded conformational change from inward-facing to occluded state. Combined with function analysis, our structures provided insights into the overall architecture, substrate coordination and inhibitor recognition mechanisms of TauT.
HIV-1 protein coding sequences are present in relevant bacteria
Authors: Pelaez-Prestel Hector F. , Mozas-Gutierrez Juan , Lafuente Esther M. , Reche Pedro A. 
Published: December 2024

ABSTRACTHuman Immunodeficiency Virus (HIV) is a retrovirus that attacks the immune system, causing acquired immunodeficiency syndrome (AIDS). Early diagnosis and treatment of HIV infected individuals are considered key to reduce HIV transmission and developing AIDS. Therefore, HIV diagnostics play an important role in the battle against AIDS. HIV tests are regarded as reliable and very specific. However, false-positive results are known to occur, usually caused by infections with unrelated pathogens leading to cross-reactive antibodies. In this work, we found through TBLASTN searches that the genome of several bacterial species, most frequentlyKlebsiella pneumoniae and Escherichia coli, contain segments matching HIV-1 proteins, including p24 and other proteins relevant for HIV testing, with a high degree of similarity (sequence identity > 95 %). The presence of HIV-1 in these bacteria of the human microbiota does not appear to be an artifact, since HIV-1 proteins were detected in different isolates of the same species. The proteome of other common viruses, particularly Influenza A virus and Hepatitis B virus, was also detected in bacterial genomes, but to a much lesser extent. Overall, our findings support that some bacteria can acquire HIV-1 genetic material and could interfere with HIV testing, causing false-positives.
Experimental monkeypox virus infection in rats
Authors: Rockx Barry , van Keulen Lucien , van der Poel Wim H.M. , Ariën Kevin K. , Vercauteren Koen , van de Water Sandra , Harders-Westerveen José , Schreur Paul J. Wichgers , van der Giessen Joke , Maas Miriam , Stockhofe Norbert , Liesenborghs Laurens 
Published: December 2024

AbstractThe global spread of Monkeypox virus (MPXV) clade IIb in 2022/2023 raised concerns about spillback into new animal reservoirs. Experimental inoculation of rats with MPXV resulted in skin lesions and viral shedding in the respiratory tract and skin. These findings suggest a potential role for rats in MPXV transmission.
Loss of Pigment Epithelium Derived Factor Sensitizes C57BL/6J Mice to Light-Induced Retinal Damage
Authors: Shelton Debresha A. , Papania Jack T. , Getz Tatiana E. , Sellers Jana T. , Giradot Preston E. , Chrenek Micah A. , Grossniklaus Hans E. , Boatright Jeffrey H. , Nickerson John M. 
Published: December 2024

5.1ABSTRACTPurposePigment epithelium-derived factor (PEDF) is a neurotrophic glycoprotein secreted by the retinal pigment epithelium (RPE) that supports retinal photoreceptor health. Deficits in PEDF are associated with increased inflammation and retinal degeneration in aging and diabetic retinopathy. We hypothesized that light-induced stress in C57BL/6J mice deficient in PEDF would lead to increased retinal neuronal and RPE defects, impaired expression of neurotrophic factor Insulin-like growth factor 1 (IGF-1), and overactivation of Galectin-3-mediated inflammatory signaling.MethodsC57BL/6J mice expressing the RPE65 M450/M450 allele were crossed to PEDFKO/KOand wildtype (PEDF+/+) littermates. Mice were exposed to 50,000 lux light for 5 hours to initiate acute damage. Changes in visual function outcomes were tracked via electroretinogram (ERG), confocal scanning laser ophthalmoscopy(cSLO), and spectral domain optical coherence tomography (SD-OCT) on days 3, 5, and 7 post-light exposure. Gene and protein expression of Galectin-3 were measured by digital drop PCR (ddPCR) and western blot. To further investigate the role of galectin-3 on visual outcomes and PEDF expression after damage, we also used a small-molecule inhibitor to reduce its activity.ResultsFollowing light damage, PEDFKO/KOmice showed more severe retinal thinning, impaired visual function (reduced a-, b-, and c-wave amplitudes), and increased Galectin-3 expressing immune cell infiltration compared to PEDF+/+. PEDFKO/KOmice had suppressed damage-associated increases in IGF-1 expression. Additionally, baseline Galectin-3 mRNA and protein expression were reduced in PEDFKO/KOmice compared to PEDF+/+. However, after light damage, Galectin-3 expression decreases in PEDF+/+mice but increases in PEDF KO/KO mice without reaching PEDF+/+levels. Galectin-3 inhibition worsens retinal degeneration, reduces PEDF expression in PEDF+/+mice, and mimics the effects seen in PEDF knockouts.ConclusionsLoss of PEDF alone does not elicit functional defects in C57BL/6J mice. However, under light stress, PEDF deficiency significantly increases severe retinal degeneration, visual deficits, Galectin-3 expression, and suppression of IGF-1 than PEDF+/+. PEDF deficiency reduced baseline expression of Galectin-3, and pharmacological inhibition of Galectin-3 worsens outcomes and suppresses PEDF expression in PEDF+/+,suggesting a novel co-regulatory relationship between the two proteins in mitigating light-induced retinal damage.
Structural analysis of tilvestamab in complex with AXL
Authors: Christakou Eleni , Lopez Andrea J. , Muruganandam Gopinath , Micklem David , Lorens James B. , Kursula Petri 
Published: December 2024

AbstractAXL is a receptor tyrosine kinase with a significant role in various biological processes and important medical implications, particularly in cancer. AXL transduces signals from the extracellular environment into the cytoplasm by binding to its ligand, growth arrest-specific protein 6 (GAS6). Activation of AXL leads to autophosphorylation of its intracellular domain and subsequent activation of downstream signaling pathways involved in cell proliferation, migration, differentiation, and survival. Tilvestamab (also known as BGB149) is a first-in-class, humanized, therapeutic anti-AXL function-blocking monoclonal antibody. We carried out a structural characterization of the AXL-tilvestamab complex, using both negative-stain and cryogenic transmission electron microscopy as well as synchrotron small-angle X-ray scattering. While AXL-Fc was highly elongated and formed large, heterogeneous complexes with the full antibody, homogeneous samples for structural studies could be made using the monomeric soluble AXL extracellular domain, the Fab fragment of tilvestamab, and an anti-Fab nanobody. Both SAXS and cryo-EM confirmed successful complex formation between the three proteins, and a low-resolution 3D model for the tilvestamab-AXL complex is presented. The data allow for sample optimization for high-resolution structural biology as well as designing mutations that could alter binding affinity and specificity.
MEMO: A Micro Memo Sensor Detecting microRNA-RISC using an Accurate Cell-Free Expression Platform
Authors: Copeland Caroline E. , Heitmeier Chloe J. , Kim Jeehye , Kwon Yong-Chan 
Published: December 2024

AbstractCirculating microRNAs have emerged as potential prognostic biomarkers of various diseases. They serve as micro memos sent out by cells, which scientists can intercept to gain real-time insights into cellular and disease status. However, establishing a standardized microRNA detection platform remains a challenge. Here, we integrate the RNA-induced silencing complex (RISC), which occupies mature microRNAs, into a complex cell-free synthetic genetic circuit using three different RNA polymerases, creating an innovative microRNA biosensor that is sensitive, precise, and cost-effective. The RISC protects the microRNA degradation during isolation and ensures the elimination of false target interactions, enhancing the detection robustness. With a limit of detection of 81 pM, affordability, and the possibility for on-demand use, this system proves to be a strong miRNA sensing tool.
Temporal and Hemispheric Dynamics in Neural Processing of Auditory and Speech Stimuli Across Linguistic Complexity: A MEG Source Space Study
Authors: Krauss Patrick , Kölbl Nikola , Müller-Voggel Nadia , Rampp Stefan , Kaltenhäuser Martin , Tzirdis Konstantin , Schilling Achim 
Published: December 2024

AbstractIn this study we investigated the neural processing of auditory stimuli of varying complexity: a non-linguistic (pure tone), a simple linguistic (phoneme) and a complex linguistic (word) stimulus. We recorded brain activity of 30 healthy, righthanded participants using magnetoencephalography (MEG), and compared the resulting evoked fields (ERFs) in source space in three different time intervals, i.e. early (0-250ms), mid (250-500ms) and late (500-750ms) responses. Our results reveal a bilateral activation during early response and rightlateralized activation in the mid-phase for all stimuli. Hoewever, the late response exhibited lateralization variations. The pure tone predominantly activated the right hemisphere, consistent with pitch processing theories. The phoneme primarily engaged the left hemisphere, supporting its role in phonemic processing. Notably, the word elicited activation in both hemispheres, reflecting phonemic processing on the left and stress patterns on the right. These findings highlight the intricate interplay between temporal processing and hemispheric lateralization in speech perception, emphasizing the importance of stimulus complexity and temporal dynamics in understanding auditory and speech processing.
Wisteria floribundaagglutinin enhancesZaire ebolavirusentry through interactions at specific N-linked glycosylation sites on the virus glycoprotein complex
Authors: Duncan Joshua D. , Pathak Monika , King Barnabas J. , Bamber Holly , Radford Paul , Dey Jayasree , Richardson Charlotte , Astbury Stuart , McClure C. Patrick , Ball Jonathan K. , Urbanowicz Richard A. , Tarr Alexander W. 
Published: December 2024

AbstractEntry ofZaireebolavirus(EBOV) into a host cell is a complex process requiring interactions between the viral glycoproteins (GP) and cellular factors. These entry factors are cell-specific and can include cell surface lectins and phosphatidylserine receptors. NPC1 is critical to the late stage of the entry process. Entry has been demonstrated to be enhanced by interactions between the virion and surface-expressed lectins, which interact with carbohydrate moieties attached to the GP. In addition, soluble lectins, including mannose binding lectin (MBL), can enhance entryin vitro. However, the mechanism of lectin-mediated enhancement remains to be defined.This study investigated the potential of three plant lectins,Wisteria floribundaagglutinin (WFA), soybean agglutinin (SBA) andGalanthus nivalisagglutinin (GNA), which possess different carbohydrate binding specificities, to enhance EBOV entry by binding to the GP. WFA was observed to potently enhance entry of lentiviral pseudotype viruses (PVs) expressing the GP of threeEbolavirusspecies (Zaire, Sudan [SUDV] and Reston [RESTV]), with the greatest impact on EBOV. SBA had a modest enhancing effect on entry that was specific to EBOV, while GNA had no impact on entry of any of theEbolavirusspecies. None of the lectins enhanced entry of control PVs expressing the surface proteins of other RNA viruses tested. WFA was demonstrated to bind directly with the EBOV-GP via the glycans, and mutational analysis implicated N238as contributing to the interaction. Furthermore, enhancement was observed in both human and bat cell lines indicating a highly conserved mechanism of action. We conclude that binding of WFA to EBOV GP through interactions including the glycan at N238results in GP alterations that enhance entry, providing evidence of a mechanism for lectin-mediated virus entry enhancement. Targeting lectin-ligand interactions presents a potential strategy for restrictingEbolavirusentry.
CENcyclopedia: Dynamic Landscape of Kinetochore Architecture Throughout the Cell Cycle
Authors: Chen Yu-Chia , Kilic Ece , Wang Evelyn , Rossman Will , Suzuki Aussie 
Published: December 2024

AbstractThe kinetochore, an intricate macromolecular protein complex located on chromosomes, plays a pivotal role in orchestrating chromosome segregation. It functions as a versatile platform for microtubule assembly, diligently monitors microtubule binding fidelity, and acts as a force coupler. Comprising over 100 distinct proteins, many of which exist in multiple copies, the kinetochore’s composition dynamically changes throughout the cell cycle, responding to specific timing and conditions. This dynamicity is important for establishing functional kinetochores, yet the regulatory mechanisms of these dynamics have largely remained elusive. In this study, we employed advanced quantitative immunofluorescence techniques to meticulously chart the dynamics of kinetochore protein levels across the cell cycle. These findings offer a comprehensive view of the dynamic landscape of kinetochore architecture, shedding light on the detailed mechanisms of microtubule interaction and the nuanced characteristics of kinetochore proteins. This study significantly advances our understanding of the molecular coordination underlying chromosome segregation.
Lean healthcare applied in emergency services: an empirical evaluation
Authors: Bonamigo Andrei , Santos Gabriel Nascimento , Chaves Sandra Maria do Amaral , Calado Robisom Damasceno 
Published: December 2024

Purpose
This study aims to analyse the setup time management using the single-minute exchange of die (SMED) method in 24 h Emergency Care Units (ECUs).

Design/methodology/approach
A total of 1,098 reports in A3 form format were analysed and grouped into analysis categories to evaluate the implications of SMED in managing setup time in the 24 h ECUs. The content analysis was based on Bardin (2011). The findings were grouped into three categories.

Findings
The findings demonstrate the contributions of the Lean Healthcare approach in the 24 h ECUs through SMED analysis to reduce setup time in activities characterised as waste in 24 h UPAs.

Research limitations/implications
In this study, data were collected directly from the Good Practices Application, from a specific project conducted in ECUs, which could generate selection bias. Finally, the datas were categorised according to the categories defined a posteriori, which may lead to interpretation bias.

Practical implications
The implications listed from the SMED perspective for setup time management allow us to guide managers, consultants, researchers, and health professionals to provide continuous improvement in 24 h ECUs. The findings can serve as a basis for reducing configuration time in other public and private healthcare service organisations.

Social implications
SMED applied in 24 h ECUs makes it possible to improve emergency services provided to society and increase the capacity to care for patients and society in general. In addition, reducing costs for health service financiers, such as government and private institutions.

Originality/value
To the best of the authors’ knowledge, this is the first study that correlates the setup time management of the SMED method in crucial areas of 24 h ECUs, demonstrating opportunities for its application in reducing time in patient journeys. The findings show the benefits of Lean in these environments and highlight several opportunities for applying SMED to reduce setup in activities characterised as waste in 24 h UPA. SMED allows for improved operational excellence in emergency units and enables target opportunities to increase user satisfaction and service capacity.
Biodiversity of key soil phylotypes is associated with increased plant richness and productivity following agricultural abandonment and afforestation
Authors: Wang Jianyu , Li Yuyu , Ji Yongbiao , He Jia , Zhang Junhong , Dong Zhenghong , Zhang Zhangxing , Xu Ran , Hu Wenhui , Fan Miaochun , Chen Wenqing 
Published: December 2024

Abstract

Anthropogenic land use modifications are causing severe degradation of terrestrial ecosystems, and multiple revegetation strategies are emerging globally to counteract the loss of plant richness and productivity. While soil microorganisms are essential for plant community dynamics, the role of soil microbial biodiversity in regulating changes in plant richness and productivity under different revegetation strategies remains unknown.

We used multitrophic co‐occurrence networks to identify soil network modules of strongly co‐occurring phylotypes along a 50‐year revegetation chronosequence of agricultural abandonment and afforestation. Soil biodiversity within these modules was related to soil nutrient cycling functions, plant richness and productivity (understorey layer in afforestation), elucidating how these network modules are associated with changes in plant richness and productivity.

Plant richness and productivity increased simultaneously following both agricultural abandonment and afforestation. However, the biodiversity of key soil taxa within distinct network modules was associated with these coupled increases through the regulation of different nutrient cycling functions. Key soil phylotypes within the network modules involved in nitrogen (N) cycling correlated with the simultaneous increase in plant richness and productivity following agricultural abandonment. In contrast, those involved in phosphorus (P) and sulphur (S) cycling were linked to the coupled responses of both plant richness and productivity under afforestation. This reflects the divergent microbial mechanisms associated with the coupled increase in plant richness and productivity along the revegetation chronosequence for both agricultural abandonment and afforestation.

Synthesis. Our findings provide correlative evidence that the biodiversity of key phylotypes within soil network modules is closely associated with the simultaneous increase in plant richness and productivity following the cessation of agricultural management. We identify key soil taxa, specific to each revegetation strategy, that could serve as potential targets for genomic and cultivation‐based approaches to counteract plant community degradation. Revegetation efforts to enhance plant richness and productivity should focus on soil phylotypes associated with N cycling after agricultural abandonment and those involved in P and S cycling during afforestation.