bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reimagining the serocatalytic model for infectious diseases: a case study of common coronaviruses
Authors: Larsen Sophie L. , Yang Junke , Lv Huibin , Huan Yang Wei , Teo Qiwen , Pholcharee Tossapol , Lei Ruipeng , Gopal Akshita B , Shao Evan K. , Talmage Logan , Mok Chris K. P. , Takahashi Saki , Kraay Alicia N. M. , Wu Nicholas C. , Martinez Pamela P. 
Published: December 2024

AbstractDespite the increased availability of serological data, understanding serodynamics remains challenging. Serocatalytic models, which describe the rate of seroconversion (gain of antibodies) and serore-version (loss of antibodies) within a population, have traditionally been fit to cross-sectional serological data to capture long-term transmission dynamics. However, a key limitation is their binary assumption on serological status, ignoring heterogeneity in optical density levels, antibody titers, and/or exposure history. Here, we implemented Gaussian mixture models - an established statistical tool - to cross-sectional data in order to characterize serological diversity of seasonal human coronaviruses (sHCoVs) throughout the lifespan. These methods identified four (NL63, 229E, OC43) to five (HKU1) distinct seropositive levels, suggesting that among seropositive individuals, the number of prior exposures or response to infection may vary. For each sHCoV, we fit adapted, multi-compartment serocatalytic models across 10 scenarios with different assumptions on exposure history and waning of antibodies. The best fit model for each sHCoV was always one that accounted for a gradient of seropositivity as well as host variation in the scale of serological response to infection. These models allowed us to estimate the strength and frequency of serological responses across sHCoVs, finding that the time for a seronegative individual to become seropositive ranges from 2.33-4.07 years across sHCoVs, and most individuals mount a strong antibody response reflected in high optical density values, skipping lower levels of seropositivity. We also find that despite frequent infection and strong serological responses, it is rare for an individual to remain seropositive throughout the lifetime. Crucially, our reimagined serocatalytic methods can be flexibly adapted across pathogens, having the potential to be broadly applied beyond this work.
Association between afterload-related cardiac performance and acute kidney injury in patients with sepsis: a retrospective cohort study
Authors: Zheng Jie-zhao , Guo Ze-bin , Li Li , Zhou Hong-xuan , Huang Jun-yu , Luo Min , Huang Min-xuan , Huo Jia-xian , Huang Wen-xing , Yuan Hao-ran , Chen Hong-xi , Jiang Zi-xin , Chen Wei-yan 
Published: December 2024

AbstractBackgroundIt is believed that there is a complex bidirectional causal and pathophysiological relationship between heart and kidney in sepsis. Afterload-related cardiac performance (ACP) has been found to have a close association with cardiac function and prognosis in sepsis. The aim of this study was to explore its correlation with sepsis-associated acute kidney injury (SA-AKI).Methods150 patients with sepsis who underwent PiCCO were included. Restricted cubic spline (RCS) and Cox proportional hazards regression were used to describe the relationship between ACP and SA-AKI. The receiver operating characteristic curve (AUROC) analysis was used to evaluate the predictive value of ACP for SA-AKI. A prediction model of SA-AKI occurrence probability within 7 days was presented by nomogram.Results67.3% patients developed SA-AKI within 7 days. The RCS model demonstrated that the risk of SA-AKI increased with the decrease of ACP. Cox regression analyses also found an independent inverse association between them (HR 0.974, 95%CI 0.963 - 0.985, p < 0.001). ACP showed significantly greater discrimination for SA-AKI than CI (p= 0.004). Independent risk factors for SA-AKI within 7 days were history of hypertension, type of pathogens, SOFA score, serum potassium and ACP. The AUROC of the nomogram established by age and the above factors was 0.865 (95%CI 0.808 – 0.923,p< 0.001) and the C-index was 0.800 (95%CI 0.753 - 0.847).ConclusionsLow ACP was associated with an increased risk of SA-AKI within 7 days. ACP, which might be superior to CI, had the potential for early prediction of SA-AKI.
Crops under continuous cultivation exhibit less plasticity than those under interrupted cultivation
Authors: Alagarasan Ganesh , Varshney Rajeev K. , Ramireddy Eswarayya 
Published: December 2024

AbstractEvolutionary studies indicate that species in stable environments often evolve with reduced plasticity, whereas those in variable environments tend to maintain higher plasticity to adapt to changing conditions. Our study explores whether this evolutionary principle extends to cultivated crops. In crop science, phenotypic plasticity is generally understood as a short-term response to environmental factors. Yet, the long-term evolutionary changes in both plastic and non-plastic traits under different cultivation regimes remain largely unexamined. Herein, we developed a novel mechanistic crop growth model, collectively termed the Trait-Environment Fitness Interaction (TEFI) Model, to study if and how trait plasticity varies among crops under different cultivation regimes. Our results, based on the TEFI Model, show higher trade-offs between fitness and plasticity. Specifically, we observed the evolution of higher plasticity in crops subjected to intermittent cultivation, which experienced more variable environments. However, this higher plasticity does not compensate for fitness losses due to the high rate of environmental unpredictability. Conversely, species under relatively stable conditions tend to evolve with reduced plasticity. Using real-world crop datasets, we validated the theoretical predictions of the TEFI Model, which suggest that the longer the interruption, the higher the plasticity. Our results highlight the evolutionary impact of cultivation patterns on trait plasticity and its importance in crop fitness. Ultimately, our findings illustrate how evolutionary principles of plasticity, as captured by the TEFI Model, can inform sustainable crop improvement strategies.
Inhibition of DKK-1 by WAY262611 Inhibits Osteosarcoma Metastasis
Authors: Tal Adit , Gunawardana-Zeigler Shimara , Peng Da , Tan Yuqi , Perez Natalia Munoz , Offenbacher Rachel , Kastner Laurel , Ciero Paul , Randolph Matthew E. , Gong Yun , Deng Hong-Wen , Cahan Patrick , Loeb David M. 
Published: December 2024

ABSTRACTOsteosarcoma (OS) is the most common primary malignant bone tumor in childhood. Patients who present with metastatic disease at diagnosis or relapse have a very poor prognosis, and this has not changed over the past four decades. The Wnt signaling pathway plays a role in regulating osteogenesis and is implicated in OS pathogenesis. DKK-1 inhibits the canonical Wnt signaling pathway, causing inhibition of osteoblast differentiation and disordered bone repair. Our lab previously demonstrated that a monoclonal antibody against DKK-1 prevented metastatic disease in a mouse model. This study expands upon those findings by demonstrating similar results with a small molecule inhibitor of DKK-1, WAY262611, bothin vitroandin vivo. WAY262611 was evaluatedin vitroon osteosarcoma cell lines, including proliferation, caspase activation, cell cycle analysis, and signaling pathway activation. We utilized our orthotopic implantation-amputation model of osteosarcoma metastasisin vivoto determine the impact of WAY262611 on primary tumor progression and metastatic outgrowth of disseminated tumor cells. Differentiation status was determined using single cell RNA sequencing. We show here that WAY262611 activates canonical Wnt signaling, enhances nuclear localization and transcriptional activity of beta-catenin, and slows proliferation of OS cell lines. We also show that WAY262611 induces osteoblastic differentiation of an OS patient-derived xenograftin vivo, as well as inhibiting metastasis. This work credentials DKK-1 as a therapeutic target in OS, allowing for manipulation of the Wnt signaling pathway and providing preclinical justification for the development of new biologics for prevention of osteosarcoma metastasis.
THE FAM53C/DYRK1A axis regulates the G1/S transition of the cell cycle
Authors: Hammond Taylar , Choi Jong Bin , Membreño Miles W. , Demeter Janos , Ng Roy , Bhattacharya Debadrita , Nguyen Thuyen N. , Hartmann Griffin G. , Bossard Carine , Skotheim Jan M. , Jackson Peter K. , Pasca Anca , Rubin Seth M. , Sage Julien 
Published: December 2024

ABSTRACTA growing number of therapies are being developed to target the cell cycle machinery for the treatment of cancer and other human diseases. Consequently, a greater understanding of the factors regulating cell cycle progression becomes essential to help enhance the response to these new therapies. Here, using data from the Cancer Dependency Map, we identified the poorly-studied factor FAM53C as a new regulator of cell cycle progression. We found that FAM53C is critical for this cell cycle transition and that it acts upstream of the CyclinD-CDK4/6-RB axis in the regulation of the G1/S transition. By mass spectrometry, biochemical, and cellular assays, we identified and validated DYRK1A as a cell cycle kinase that is inhibited by and directly interacts with FAM53C. DYRK1A kinase inhibition rescues the G1 arrest induced by FAM53C knock-down. Consistent with the role for FAM53C identified in cells in culture,FAM53Cknockout human cortical organoids display increased cell cycle arrest and growth defects. In addition,Fam53Cknockout mice show defects in body growth and behavioral phenotypes. Because DYRK1A dysregulation contributes to developmental disorders such as Down syndrome as well as tumorigenesis, future strategies aiming at regulating FAM53C activity may benefit a broad range of patients.
Complex opioid driven modulation of glutamatergic and cholinergic neurotransmission in a GABAergic brain nucleus associated with emotion, reward and addiction
Authors: Chittajallu R. , Vlachos A. , Yuan X.Q. , Hunt S. , Abebe D. , London E. , Pelkey KA. , McBain C.J. 
Published: December 2024

ABSTRACTThe medial habenula (mHb)/interpeduncular nucleus (IPN) circuitry is resident to divergent molecular, neurochemical and cellular components which, in concert, perform computations to drive emotion, reward and addiction behaviors. Although housing one of the most prominent mu opioid receptor (mOR) expression levels in the brain, remarkably little is known as to how they impact mHb/IPN circuit function at the granular level. In this study, our systematic functional and pharmacogenetic analyses demonstrate that mOR activation attenuates glutamatergic signaling whilst producing an opposing potentiation of glutamatergic/cholinergic co-transmission mediated by mHb substance P and cholinergic neurons, respectively. Intriguingly, this latter non-canonical augmentation is developmentally regulated only emerging during later postnatal stages. Further, specific potassium channels act as a molecular brake on nicotinic receptor signaling in the IPN with the opioid mediated potentiation of this arm of neurotransmission being operational only following attenuation of Kv1 function. Thus, mORs play a remarkably complex role in modulating the salience of distinct afferent inputs and transmitter modalities that ultimately influences synaptic recruitment of common downstream GABAergic IPN neurons. Together, these observations provide a framework for future investigations aimed at identifying the neural underpinnings of maladaptive behaviors that can emerge when endogenous or exogenous opioids, including potent synthetic analogs such as fentanyl, modulate or hijack this circuitry during the vulnerable stages of adolescence and in adulthood.
The Role of BAZ2-dependent Chromatin Remodeling in Suppressing G4 DNA Structures and Associated Genomic Instability
Authors: Vandeuren Adrianna L. , O’Dare Kierney , Wilson Rosemary H. C. , van Eijk Patrick , Julio Lindsay R. , MacLeod Shannon G. , Chee Ella , Salpukas Annika , Kriz Emma M. , Lantz George A. , Gordon Shellaina , Elsässer Simon J. , Reed Simon H. , Day Tovah A. 
Published: December 2024

AbstractDNA G-quadruplexes (G4s) are secondary structures with significant roles in regulating genome function and stability. Dysregulation of the dynamic formation of G4s is linked to genomic instability and disease, but the underlying mechanisms are not fully understood. In this study, we conducted a screen of chromatin-modifying enzymes and identified nine potential inhibitors of G4 formation, including seven that were not previously characterized. Among these, we highlight the role of BAZ2 chromatin remodelers as key suppressors of G4 DNA and G4-related genome instability. Depletion of BAZ2 subunits led to increased G4 formation, especially at transcriptional regulatory elements. BAZ2B was found to associate with G4 loci, suggesting that it plays a direct role in suppressing G4s. While BAZ2-deficient cells exhibited modest genomic instability, treatment with the G4-stabilizing ligand BRACO19 exacerbated double-strand breaks (DSBs), highlighting its utility as a tool to study G4-dependent genome instability. DSB profiling using INDUCE-seq uncovered distinct breakage patterns around G4s, further underscoring the impact of G4s on genome integrity. Notably, we found that within G4s, G repeats were more susceptible to DSBs than loops. These results establish BAZ2 chromatin remodeling complexes as direct regulators of G4 dynamics and provide new insights into G4-dependent genome instability.
Monoclonal antibodies targeting the FimH adhesin protect against uropathogenicE. coliUTI
Authors: Lopatto Edward D. B. , Santiago-Borges Jesús M. , Sanick Denise A. , Malladi Sameer Kumar , Azimzadeh Philippe N. , Timm Morgan W. , Fox Isabella F. , Schmitz Aaron J. , Turner Jackson S. , Ahmed Shaza Sayed , Ortinau Lillian , Gualberto Nathaniel C. , Pinkner Jerome S. , Dodson Karen W. , Ellebedy Ali H. , Kau Andrew L. , Hultgren Scott J. 
Published: December 2024

AbstractAs antimicrobial resistance increases, urinary tract infections (UTIs) are expected to pose an increased burden in morbidity and expense on the healthcare system, increasing the need for alternative antibiotic-sparing treatments. Most UTIs are caused by uropathogenicEscherichia coli(UPEC), whileKlebsiella pneumoniaecauses a significant portion of non-UPEC UTIs. Both bacteria express type 1 pili tipped with the mannose-binding FimH adhesin critical for UTI pathogenesis. We generated and biochemically characterized 33 murine monoclonal antibodies (mAbs) to FimH. Two mAbs protected mice fromE. coliUTI. Mechanistically, we show that this protection is Fc-independent and mediated by the ability of these mAbs to sterically block FimH function. Our data reveals that FimH mAbs hold promise as an antibiotic-sparing treatment strategy.
Relationship between concentration of cytokinin for efficient shoot regeneration and seed coat color in leaf lettuce
Authors: Kimura Mitsuhiro , Yoshizumi Takeshi 
Published: December 2024

AbstractLettuce (Lactuca sativaL.) is an economically important leafy vegetable crop around the world. Recently, transgenic lettuce has been developed to improve agronomic traits. Although plant regeneration is a key step in plant genetic transformation, it depends strongly on the cultivar. In this study, shoot regeneration efficiency was measured by using two leaf lettuce cultivars, ‘Chima-sanchi’, white seed cultivar, and ‘Chirimen-chisya’, brown seed cultivar, a basal salt mixture, and a combination of the cytokinin, 6-benzylaminopurine (BAP), and an auxin, 1- naphthaleneacetic acid (NAA). Efficient shoot regeneration in ‘Chima-sanchi’ was thus obtained on 1 x Murashige and Skoog medium (MS) with 0.05 mg L-1BAP and 0.1 mg L-1NAA. However, the highest efficiency was obtained in ‘Chirimen-chisya’ on 1 x MS with 0.5 mg L-1BAP and 0.1 mg L-1NAA. Therefore, the BAP concentration for efficient shoot regeneration differs significantly between the two cultivars. These cultivars also have different seed coat colors. Due to the similar results obtained from analyzing 4 additional cultivars, 2 white seed cultivars and 2 brown seed cultivars, we demonstrated a strong correlation between the BAP concentration for efficient shoot regeneration and the seed coat color in leaf lettuce.
Pex3 promotes formation of peroxisome-peroxisome and peroxisome-lipid droplet contact sites
Authors: Amado Lucía , Franzkoch Rico , Percifull Louis , Flatemersch Vico , Brüggermann Eleni Joana , Psathaki Olympia Ekaterini , Schuldiner Maya , Bohnert Maria , Bülow Margret , Montoro Ayelén González 
Published: December 2024

ABSTRACTPeroxisomes are ubiquitous organelles that mediate central metabolic functions, such as fatty acid β-oxidation, as well as diverse tissue- and organism-specific processes. Membrane contact sites, regions of close apposition with other organelles for direct communication, are central to several aspects of their life cycle. Pex3 is a conserved multifunctional peroxisomal transmembrane protein involved in the insertion of peroxisomal membrane proteins, in pexophagy, and in the formation of membrane contact sites. Here, we show that elevated Pex3 levels inSaccharomyces cerevisiaeinduce the formation of peroxisome clusters surrounded by lipid droplets, mediated by peroxisome-peroxisome and peroxisome-lipid droplet contact sites. This clustering occurs independently of Pex3 partners in other processes, Pex19, Inp1, and Atg36. The cytosolic domain of Pex3 binds peroxisomes, suggesting a direct role in homotypic contact site formation. Lipid droplet-peroxisome contact sites require the lipid droplet-localized triacylglycerol lipase Tgl4, which is enriched along with other lipases at this interface. Pex3 overexpression inDrosophila melanogaster similarly alters peroxisome and lipid droplet morphology and promotes contact site formation. Together, our results offer novel molecular insights into homotypic peroxisome contact sites and peroxisome-lipid droplet contact sites across species.
Resolving the design principles that control postnatal vascular growth and scaling
Authors: Pi Danielle , Braun Jonas , Dutta Sayantan , Patra Debabrata , Bougaran Pauline , Mompeón Ana , Ma Feiyang , Stock Stuart R , Choi Sharon , García-Ortega Lourdes , Pratama Muhammad Yogi , Pichardo Diomarys , Ramkhelawon Bhama , Benedito Rui , Bautch Victoria L , Ornitz David M , Goyal Yogesh , Iruela-Arispe M. Luisa 
Published: December 2024

SUMMARYAfter birth, tissues grow continuously until reaching adult size, with each organ exhibiting unique cellular dynamics, growth patterns, and (stem or non-stem) cell sources. Using a suite of experimental and computational multiscale approaches, we found that aortic expansion is guided by specific biological principles and scales with the vertebral column rather than animal body weight. Expansion proceeds via two distinct waves of arterial cell proliferation along blood flow that are spatially stochastic, yet temporally coordinated. Each wave exhibits unique cell cycle kinetics and properties, with the first wave exhibiting cell cycle durations as fast as 6 hours. Single-cell RNA sequencing showed changes in fatty acid metabolism concomitant with an increase in cell size. Mathematical modeling and experiments indicated endothelial cell extrusion is essential for homeostatic aortic growth and balancing excess proliferation. In a genetic model of achondroplasia, the aorta achieves proper scaling through enhanced cell extrusion while maintaining normal proliferation dynamics. Collectively, these results provide a blueprint of the principles that orchestrate aortic growth which depends entirely on differentiated cell proliferation rather than resident stem cells.
The effect of speech masking on the human subcortical response to continuous speech
Authors: Polonenko Melissa J. , Maddox Ross K. 
Published: December 2024

AbstractAuditory masking—the interference of the encoding and processing of an acoustic stimulus imposed by one or more competing stimuli—is nearly omnipresent in daily life, and presents a critical barrier to many listeners, including people with hearing loss, users of hearing aids and cochlear implants, and people with auditory processing disorders. The perceptual aspects of masking have been actively studied for several decades, and particular emphasis has been placed on masking of speech by other speech sounds. The neural effects of such masking, especially at the subcortical level, have been much less studied, in large part due to the technical limitations of making such measurements. Recent work has allowed estimation of the auditory brainstem response (ABR), whose characteristic waves are linked to specific subcortical areas, to naturalistic speech. In this study, we used those techniques to measure the encoding of speech stimuli that were masked by one or more simultaneous other speech stimuli. We presented listeners with simultaneous speech from one, two, three, or five simultaneous talkers, corresponding to a range of signal-to-noise ratios (SNR; Clean, 0, −3, and −6 dB), and derived the ABR to each talker in the mixture. Each talker in a mixture was treated in turn as a target sound masked by other talkers, making the response quicker to acquire. We found consistently across listeners that ABR wave V amplitudes decreased and latencies increased as the number of competing talkers increased.Significance statementTrying to listen to someone speak in a noisy setting is a common challenge for most people, due to auditory masking. Masking has been studied extensively at the behavioral level, and more recently in the cortex using EEG and other neurophysiological methods. Much less is known, however, about how masking affects speech encoding in the subcortical auditory system. Here we presented listeners with mixtures of simultaneous speech streams ranging from one to five talkers. We used recently developed tools for measuring subcortical speech encoding to determine how the encoding of each speech stream was impacted by the masker speech. We show that the subcortical response to masked speech becomes smaller and increasingly delayed as the masking becomes more severe.
Bacterial Lytic Polysaccharide Monooxygenases negatively affect insect larvae growth
Authors: Baranek Jakub , Wojtkowiak Filip , Belińska Kinga , Wojtkowiak Paulina , Zielezinski Andrzej 
Published: December 2024

AbstractBACKGROUNDLytic Polysaccharide Monooxygenases (LPMOs) are recently discovered redox enzymes broadly distributed across various taxa, including bacteria, fungi, and viruses. LPMO proteins can oxidatively cleave the glycosidic chains found in carbohydrate polymers, allowing efficient decomposition of recalcitrant polysaccharides such as chitin or cellulose. While LPMOs have primarily been studied for their role in biomass conversion, other biological roles of these enzymes are not well understood.RESULTSHere, we assess the influence of four different LMPOs, derived fromBacillus thuringiensisandSerratia marcescensbacteria, onSpodoptera exigualarvae. The tested proteins administeredper osresulted in significant growth impairment, with the mean body weight of the treated larvae being lower than the control group by 30-69 percentage points, depending on the specific LPMO.CONCLUSIONThis work indicates that LPMO enzymes are capable of insect larvae development inhibition and thus may play an important role in insect pathogenesis caused by bacteria. Moreover, the results obtained in this study are an early sign of the potential use of LPMOs in future pest management strategies.