bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cool ocean temperatures fail to buffer the impacts of heat exposure during low tide on the behaviour and physiology of a keystone predator
Authors: Walton Lydia N. , Watts Viola R. , Schuster Jasmin M. , Bates Amanda E. 
Published: March 2024

AbstractAir temperatures are warming at faster rates than ocean temperatures, and this “land-sea warming contrast” may create reprieves from thermal stress by providing cool underwater refugia during extreme heat events. Here we tested the impacts of the “land-sea warming contrast” on physiology (metabolism) and behaviour (feeding) in the juvenile life stage of a keystone intertidal predator,Pisaster ochraceus, by experimentally manipulating air (∼20℃, 25℃, 30℃) and water (∼15℃, 20℃) temperatures (at independent rates) representing early summer, late summer, and heatwave conditions in Barkley Sound (British Columbia, Canada). We further made observations of air temperatures, sea surface temperatures, andPisastermoribundity at our study location to support interpretation of our results. We predicted metabolism and feeding would increase with early and late summer temperatures, but decrease during heatwave conditions as animals surpass their thermal optimum. We observed the greatest mortality and lowest feeding in juvenilePisasterexposed to cool ocean temperatures (∼15℃) and high aerial temperatures typical of extreme heat events (∼30℃). Feeding rates increased with heat stress duration, indicating animals may be compensating for elevated metabolism. Metabolic rates did not differ between air temperatures, but oxygen consumption was higher in animals with access to mussels than forPisasterthat were fasted. The highest levels of experimental and field moribundity were observed in August, indicatingPisastermay have accumulated physiological stress damage following elevated air and ocean temperatures throughout the summer. Our research implicates shifts in community dynamics due to the loss of this keystone species as air temperatures warm.Summary StatementCooler ocean temperatures, rather than creating thermal refugia, may cause physiological stress for juvenilePisaster ochraceusexposed to warm air during low tide.
Labeling Natural Killer cells with superparamagnetic iron oxide nanoparticles for detection by preclinical and clinical-scale magnetic particle imaging
Authors: Sehl Olivia C. , Yang Yanwen , Anjier Ariana R , Nevozhay Dmitry , Cheng Donghang , Guo Kelvin , Fellows Benjamin , Mohtasebzadeh A. Rahman , Mason Erica E. , Sanders Toby , Kim Petrina , Trease David , Koul Dimpy , Goodwill Patrick W. , Sokolov Konstantin , Wintermark Max , Gordon Nancy , Greve Joan M. , Gopalakrishnan Vidya 
Published: March 2024

AbstractIntroductionClinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) for the detection, localization, and quantification of VivoTrax-labeled NK cells.MethodsHuman-derived NK-92 cells were labeled by co-incubation with VivoTrax for 24 hours then the excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled vs. unlabeled NK-92 cells was assessed after 4 hours of co- incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17) using bioluminescent or GFP counts. Labeled NK-92 cells at two different doses (0.5 or 1 x 106) were administered to excised mouse brains (cerebellum), tibias, and lungs then imaged by 3D preclinical MPI (MOMENTUM imager) and localized relative to fiducial markers. NK-92 cells were imaged by clinical-scale MPI under development at Magnetic Insight Inc.ResultsNK-92 cells were labeled with an average of 3.17 pg Fe/cell with no measured effects on cell viability or cytolytic activity against 3 tumor cell lines. MPI signal was directly quantitative with the number of VivoTrax-labeled NK-92 cells, with preclinical limit of detection of 3.1 x 104cells on MOMENTUM imager. Labeled NK-92 cells could be accurately localized in mouse brains, tibias, and lungs within < 1 mm of stereotactic injection coordinates with preclinical scanner. Feasibility for detection of a clinically relevant dose of 4 x 107labeled NK-92 cells was demonstrated on clinical-scale MPI.ConclusionMPI can provide sensitive, quantitative, and accurate spatial information on NK cell delivery, showing its potential to resolve a significant unmet clinical need to track NK cell treatments in patients.
Understanding the binding mechanisms of Alzheimer risk factor TREM2 in lipid bilayer using multi-scale molecular dynamics simulations
Authors: Zhong Zhiwen , Ulmschneider Martin , Lorenz Christian D. 
Published: March 2024

AbstractAlzheimer’s disease (AD) is a widespread neurodegenerative condition affecting millions globally. Recent research has implicated variants of the triggering receptor ex-pressed in myeloid cells 2 (TREM2) as risk factors for AD. TREM2, an immunomodula-tory receptor on microglial surfaces, plays a pivotal role in regulating microglial activa-tion by associating with DNAX-activation protein 12 (DAP12). Despite its significance, the mechanism underlying the formation of the complex between the transmembrane domains (TMDs) of TREM2 and DAP12 remains unclear. This study employs multi-scale molecular dynamics (MD) simulations to investigate three TMD complex models, including two derived from experiments and one generated by AlphaFold2. Conducted within a lipid membrane consisting of an 80:20 mixture of phosphatidylcholine (POPC) and cholesterol, our analysis reveals hydrogen bonding interactions between K26 of TREM2 and D16 of DAP12 in all three models, consistent with previous experimen-tal findings. Our results elucidate the different spatial conformations observed in the models and offer insights into the structure of the TREM2/DAP12 TMD complex. Furthermore, we elucidate the role of charged residues in the assembly structure of the complex within the lipid membrane. These findings enhance our understanding of the molecular mechanism governing TREM2/DAP12 complex formation, providing a foundation for designing novel therapeutic strategies to address AD and other neu-rodegenerative diseases.Graphical AbstractHighlightsDifferent TREM2/DAP12 complexes are generated using experimental PDB structures or AlphaFold2Long time coarse-grained MD simulations are used for getting the sys-tems stableAtomistic detailed complex structures are captured using all-atom sim-ulationProvides mechanistic insight into TREM2 transformation from its un-bound state to bounded stateOffers novel insights into the molecular basis of TREM2/DAP12 sig-nalling pathway
Effect of Electroacupuncture Pretreatment on Cognitive Impairment and Mitophagy in Aging Model Rats and its mechanism
Authors: Liu Biyong , Tan Tiantian , Liu Jianmin , Li Zhijie , Feng Qunhu , Qiu Su , Xiong Chengkai , Liu Qing , Li Jialin , Li Yihong 
Published: March 2024

AbstractObjectiveInvestigate the effects of "Shuanggu Yitong" EA pretreatment on cognitive impairment, mitochondrial function, and mitophagy in aging model rats, and to analyze the related mechanisms.MethodsForty 3-month-old male SD rats were randomly divided into a blank group, a model group, an EA group, and a sham EA group, with 10 rats in each group. And the Morris water maze test was performed after the intervention. HE staining, to observe the morphological changes of the hippocampus of the model rats. Nissl staining was used to observe the changes in the number of hippocampal neurons in rats, Western Blotting (WB) was used to observe the expression of endogenous PTEN-induced hypothetical kinase 1 (PINK1) and human Parkinson’s protein 2 (Parkin) in the hippocampus, spectrophotometry was employed to detect the activity of respiratory chain complex I in the hippocampus of the model rats, and flow cytometry was utilized to detect hippocampal mitochondrial membrane potential (MMP) and hippocampal mitochondrial permeability transition pore (MPTP) opening.Results"Shuanggu Yitong" EA pretreatment relieved the cognitive impairment induced by D-galactose in subacute aging model rats. The mechanism of "Shuanggu Yitong" EA pretreatment in the improvement of cognitive impairment of subacute aging model rats may be related to the enhancement of Pink1/Parkin mediated mitophagy and the timely removal of accumulated abnormal mitochondria, thus improving mitochondrial function.Conclusion"Shuanggu Yitong" EA pretreatment can significantly improve the cognitive impairment induced by D-galactose in subacute aging model rats.
Alcohol, smoking, and illicit substance use in Cameroon: unveiling related risk factors among university students in Yaoundé
Authors: Lekeumo Cheuyem Fabrice Zobel , Edzamba Michel Franck , Amani Adidja , Mossus Tatiana 
Published: March 2024

AbstractBackgroundSubstance use, including alcohol, tobacco and illicit drugs, is a growing public health problem worldwide. There is a rapid increase in substance use among young adults in many sub-Saharan African countries. This study aimed to assess the factors associated with the use of different psychoactive substances among university students in Yaoundé.MethodsA cross-sectional and analytical study was conducted from September to October 2023 at Yaoundé 1 University in Cameroon. All eligible students aged 18 years and older who gave written informed consent were included. A convenience nonprobability sampling method was used to recruit consenting students. The data collectors were medical students who were trained for 2 days and given appropriate instructions before the survey. The data collected were reviewed and checked for completeness before being entered. The data were analyzed using Statistics 4.3.1.ResultsA total of 191 university students were enrolled in the study. Age (p-value=0.002), level of study (p-value=0.048), and smoking status (p-value=0.005) of the participants were significant factors associated with alcohol on univariate analysis. Multivariate logistic regression showed that students aged 20-25 years were significantly 2.9 times more likely to drink alcohol than those aged less than 20 years (p-value=0.003). Students who smoke were 2.7 times more likely to drink alcohol than those who do not smoke (p-value=0.008). Living situation (p=0.013) and drug use status (p-value<0.0001) were significant factors associated with smoking on univariate analysis. On multivariate analysis, drug users were 3.2 times more likely to smoke than drug non-users (p-value<0.0001). Drug use was significantly associated with district of residence of consumer on univariate analysis (p-value=0.024). Living situation (p-value=0.016), faculty/school(p-value=0.04), and district of residence (p-value=0.037) were significantly associated with polysubstance use. Students living in shared accommodation were 3.8 times more likely to be polysubstance users than those living with their families (p-value=0.023). Almost all smokers (95.1%) reported being aware the of the psychosocial, mental and health consequences of substance use (p-value=0.021).ConclusionSeveral factors have been associated with substance use among college students. These sociodemographic factors can help to strategize and implement tailored interventions to reduce the risk of subsequent substance dependence and other harmful consequences.
Human primosome requires replication protein A when copying DNA with inverted repeats
Authors: Baranovskiy Andrey G. , Morstadt Lucia M. , Romero Eduardo E. , Babayeva Nigar D. , Tahirov Tahir H. 
Published: March 2024

ABSTRACTThe human primosome, a four-subunit complex of primase and DNA polymerase alpha (Polα), initiates DNA synthesis on both chromosome strands by generating chimeric RNA-DNA primers for loading DNA polymerases delta and epsilon (Polε). Replication protein A (RPA) tightly binds to single-stranded DNA strands, protecting them from nucleolytic digestion and unauthorized transactions. We report here that RPA plays a critical role for the human primosome during DNA synthesis across inverted repeats prone to hairpin formation. On other alternatively structured DNA, forming a G-quadruplex, RPA does not assist primosome. A stimulatory effect of RPA on DNA synthesis across hairpins was also observed for the catalytic domain of Polα but not of Polε. The winged helix-turn-helix domain of RPA is essential for an efficient hairpin bypass and increases RPA-Polα cooperativity on the primed DNA template. Cryo-EM studies revealed that this domain is mainly responsible for the interaction between RPA and Polα. The flexible mode of RPA-Polα interaction during DNA synthesis implies the mechanism of template handover between them when the hairpin formation should be avoided. This work provides insight into a cooperative action of RPA and primosome on DNA, which is critical for DNA synthesis across inverted repeats.SIGNIFICANCEThis work revealed the critical role of RPA during DNA synthesis across inverted repeats by the human primosome. It was shown that a small winged helix-turn-helix domain of RPA is essential for the cooperative action of RPA and primosome, especially when copying DNA sequences prone to hairpin structure formation. Structural studies uncovered the mode of RPA and Polα integration, which assures an efficient DNA handover between them. This work provides a notable insight into the early steps of Okazaki fragments synthesis.
Structural basis of substrate transport and drug recognition by the human thiamine transporter SLC19A3
Authors: Gabriel Florian , Spriestersbach Lea , Fuhrmann Antonia , Jungnickel Katharina E. J. , Mostafavi Siavash , Pardon Els , Steyaert Jan , Löw Christian 
Published: March 2024

AbstractThiamine (vitamin B1) functions as an essential coenzyme in cells. Humans and other mammals cannot synthesise this vitaminde novoand thus have to take it up from their diet. Eventually, every cell needs to import thiamine across its plasma membrane which is mainly mediated by two specific thiamine transporters SLC19A2 and SLC19A3. Loss of function mutations in either of these transporters leads to detrimental, life-threatening metabolic disorders. SLC19A3 is furthermore a major site of drug interactions. Many medications, including antidepressants, antibiotics and chemotherapeutics are known to inhibit this transporter, with potentially fatal consequences for patients. Despite a thorough functional characterisation over the past two decades, the structural basis of its transport mechanism and drug interactions has remained elusive. Here, we report eight cryo-electron microscopy (cryo-EM) structures of the human thiamine transporter SLC19A3 in complex with various ligands. Conformation-specific nanobodies enabled us to capture different states of SLC19A3’s transport cycle, revealing the molecular details of thiamine recognition and transport. We identified nine novel drug interactions of SLC19A3 and determined structures of the transporter in complex with the inhibitors fedratinib, hydroxychloroquine, amprolium and amitriptyline. These data allow us to develop an understanding of the transport mechanism and ligand recognition of SLC19A3.
Targeted protein degradation of the CPSF complex by benzoxaboroles through sumoylation
Authors: Zhang Ning , Samad Abdul , Zahedifard Farnaz , Wall Richard J. , Horn David , Zoltner Martin , Field Mark C. 
Published: March 2024

AbstractBenzoxaboroles (BoBs) feature a boron-heterocyclic core and are an important innovation in the development of drugs against a range of pathogens and other pathologies. A broad spectrum of pharmacology is associated with chemically diverse BoB derivatives and includes multiple modes-of-action (MoA) and targets. However, a consensus MoA for BoBs targeting evolutionarily diverse protozoan pathogens has emerged with the identification of CPSF3/CPSF73 in the CPSF complex in both apicomplexan and kinetoplastida parasites. Here we establish a functional connection between protein sumoylation and the boron-heterocyclic scaffold shared by all BoBs using comprehensive genetic screens inTrypanosoma brucei.There is a rapid temporal and spatial shift in global protein sumoylation following BoB exposure and members of the CPSF complex are specifically destabilised in a SUMO and proteosome-dependent manner. Finally, we find rapid decrease in bulk mRNA levels, consistent with the role of CPSF3 in mRNA maturation. We propose that a combination of direct inhibition coupled with targeted degradation of CPSF3 underpins the specificity of BoBs against trypanosomatids.
Combinatorial control of type IVa pili formation by the four polarized regulators MglA, SgmX, FrzS and SopA
Authors: Oklitschek Michel , Carreira Luís António Menezes , Muratoğlu Memduha , Søgaard-Andersen Lotte , Treuner-Lange Anke 
Published: March 2024

AbstractType IVa pili (T4aP) are widespread and enable bacteria to translocate across surfaces. T4aP engage in cycles of extension, surface adhesion and retraction, thereby pulling cells forward. Accordingly, the number and localization of T4aP are critical to efficient translocation. Here, we address how T4aP formation is regulated inMyxococcus xanthus, which translocates with a well-defined leading and lagging cell pole using T4aP at the leading pole. This localization is orchestrated by the small GTPase MglA and its downstream effector SgmX that both localize at the leading pole and recruit the PilB extension ATPase to the T4aP machinery at this pole. Here, we identify the previously uncharacterized protein SopA and show that it interacts directly with SgmX, localizes at the leading pole, stimulates polar localization of PilB, and is important for T4aP formation. We corroborate that MglA also recruits FrzS to the leading pole, and that FrzS stimulates SgmX recruitment. In addition, FrzS and SgmX separately recruit SopA. Precise quantification of T4aP formation and T4aP-dependent motility in various mutants support a model whereby the main pathway for stimulating T4aP formation is the MglA/SgmX pathway. FrzS stimulates this pathway by recruiting SgmX and SopA. SopA stimulates the MglA/SgmX pathway by stimulating the function of SgmX, likely by promoting the SgmX-dependent recruitment of PilB. The architecture of the MglA/SgmX/FrzS/SopA protein interaction network for orchestrating T4aP formation allows for combinatorial regulation of T4aP levels at the leading cell pole resulting in discrete levels of T4aP-dependent motility.
A Novel Cell Culture Scratch Assay Platform Generates Reproducible Gaps for Quantitative Cell Movement-Based Studies
Authors: Wolpert Nicholas , Gollahon Lauren 
Published: March 2024

AbstractScratch assays are routinely performed for multiple research applications in cell biology (i.e., migration, metastasis, repair mechanisms, etc.). Conventional scratches are usually generated with pipette tips. User inconsistencies and varying pipette tips are major obstacles to reproducibility and quantitative power. Here, we present a novel, scratch/gap generating, cell culture plate-based, platform that addresses these issues, providing consistency and reproducibility across multiple users, significantly reducing variability, and increasing quantitative outcomes.
Bacterial strain nomenclature in the genomic era: Life Identification Numbers using a gene-by-gene approach
Authors: Palma Federica , Hennart Melanie , Jolley Keith A. , Crestani Chiara , Wyres Kelly L. , Bridel Sebastien , Yeats Corin A. , Brancotte Bryan , Raffestin Brice , David Sophia , Lam Margaret M. C. , Izdebski Radosław , Passet Virginie , Rodrigues Carla , Rethoret-Pasty Martin , Maiden Martin C. J. , Aanensen David M. , Holt Kathryn E. , Criscuolo Alexis , Brisse Sylvain 
Published: March 2024

AbstractUnified strain taxonomies are crucial for fostering international communication in microbiological research and for the epidemiological surveillance of bacterial pathogens. While multilocus sequence typing (MLST) has served as a foundation of strain taxonomy for two decades, whole genome sequencing enables more precise classifications and significantly improves discriminatory resolution. The core genome-wide extension of MLST (known as cgMLST) thus holds great promise for strain genotyping and classification, but its implementation faces challenges that include missing data, potential instability of cluster-based nomenclatures, and the necessity to ensure backwards compatibility with MLST identifiers. Life Identification Number (LIN) codes offer a solution by providing multi-level classification groups that are inherently stable. Here, we present, consolidate, and extend the cgMLST-based LIN code approach. We first develop a nicknaming system for LIN code prefixes, which enables flexible human-readable strain nomenclatures. UsingKlebsiella pneumoniae(Kp) as an example, LIN code nicknames were attributed by inheritance from MLST identifiers, thus perpetuating the legacy of MLST nomenclatures in the genomic era. We show that while 7-gene MLST sometimes conflates unrelated sublineages into the same ST, cgMLST-based LIN codes are highly concordant with phylogenetic relationships. We implement this novel LIN code-based nomenclature in the BIGSdb platform, and illustrate, with Pathogenwatch, how it can also be used in other genomic epidemiology platforms. Finally, we demonstrate the value of LIN codes for tracking the strain diversity within high-risk internationally disseminated clonal groups of Kp and protracted outbreaks. Given its stability, precision, and flexibility, we recommend the adoption of the cgMLST-based LIN code taxonomic approach for Kp and suggest that this approach is widely applicable to other bacterial pathogens.
Evidence for unfolded Fermi surfaces in the charge-density-wave state of kagome metal FeGe revealed by de Haas–van Alphen effect
Authors: Tang Kaixin , Zhou Hanjing , Li Houpu , Pan Senyang , Wu Xueliang , Li Hongyu , Zhang Nan , Xi Chuanying , Zhang Jinglei , Wang Aifeng , Wan Xiangang , Xiang Ziji , Chen Xianhui 
Published: March 2024

The antiferromagnetic kagome lattice compound FeGe has been revealed to host an emergent charge-density-wave (CDW) state which manifests complex interplay between the spin, charge, and lattice degrees of freedom. Here, we present a comprehensive study of the de Haas–van Alphen effect by measuring torque magnetometry under magnetic fields up to 45.2 T to map Fermi surfaces in this unusual CDW state. For a field along the c direction, we resolve four cyclotron orbits, with the largest one roughly corresponding to the area of the 2×2 folded Brillouin zone. Three smaller orbits are characterized by light effective cyclotron masses in the range of (0.18–0.30)me. Angle-resolved measurements identify one Fermi surface segment with weak anisotropy. Combined with band structure calculations, our results suggest that features of unfolded Fermi surfaces are robust against CDW reconstruction, corroborating the unconventional effect of a short-ranged CDW on the electronic structure.

Published by the American Physical Society
2024